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1. Efficacy and safety of panitumumab in a cohort of patients with metastatic colorectal cancer in France: PANI OUEST, a post–EMA-approval descriptive study with a geriatric oncology focus

Author

Zarrin Alavi, Véronique Guérin Meyer, Olivier Dupuis, Jean-François Ramée, Oana Cojocarasu, Fanny Marhuenda, A. Gourlaouen, Philippe Deguiral, Jean-Philippe Metges, Loïc Campion, Herve Desclos, Isabelle Cumin, Delphine Deniel Lagadec, F. Grude, Remy Barraya, V. Klein, Yann Touchefeu, Julien Edeline, Aurelie Fichet, Jean-Yves Douillard, Hélène Senellart, Xavier Artignan, Karine Bideau, Roger Faroux, Nach Eddine Achour, Marc Porneuf, Claire Stampfli, and Dominique Besson

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Colorectal cancer, Medical Oncology, Proto-Oncogene Proteins p21(ras), Antineoplastic Agents, Immunological, Internal medicine, Pharmacovigilance, Product Surveillance, Postmarketing, medicine, Humans, Panitumumab, Progression-free survival, Aged, Aged, 80 and over, business.industry, Gastroenterology, Cancer, Middle Aged, medicine.disease, Progression-Free Survival, Irinotecan, Treatment Outcome, Geriatric oncology, Geriatrics, Cohort, Female, Original Article, France, Colorectal Neoplasms, business, medicine.drug
Abstract

Background/aims The Bretagne-Pays de la Loire cancer observatory, an oncology network created by the French Ministry of Health, is specifically dedicated to assess the use of new targeted anticancer therapies in routine practice. In line with the French National Cancer III program, our cancer network set up a real-life cohort, which is independent of the pharmaceutical industry, for patients with colorectal cancer to monitor patient safety and quality of care and promote pharmacovigilance. Materials and methods Panitumumab monotherapy was assessed in 243 patients with wild-type Kirsten rat sarcoma who were treated for metastatic colorectal cancer (mCRC) between July 2008 and December 2010 after prior chemotherapy using oxaliplatine and irinotecan. This was a post-European medicine agency marketing (EMA-M) study Results: This study shed light on the best practices, strategic adaptations, clinical results (treatment objective responses, 13%; progression free survival, 2.99 months [2.73-3.15]; and overall survival, 6.8 months [5.49-8.38]) as well as expected or unexpected (grade 3 or 4: 11.5%) secondary effects in the phase IV panitumumab treatment of mCRC. Conclusion Our results are similar to those by Amado whose phase III study led to obtaining EMA-M for panitumumab and tend to confirm the antitumor activity of this antiepidermal growth factor receptor antibody in the treatment of mCRC. In addition, our results opened avenues to further assessment of panitumumab use as monotherapy as well as its benefit-risk ratio while taking into account the patients' general and clinical characteristics. In 2012, the French National Authority for Health appended these data to the panitumumab transparency committee report.

Published
2020

2. Nal-IRI/LV5-FU versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI)-PRODIGE 62: A multicentre, randomised, non-comparative phase II study

Author

Laetitia Dahan, Emilie Barbier, David Tougeron, Jean Philippe Metges, Samy Louafi, Christophe Borg, Roger Faroux, Lila Gaba, Christophe Louvet, Jérôme Desramé, Astrid Lièvre, Violaine Randrian, Frédéric Di Fiore, Sylvain Manfredi, Antoine Adenis, Gilles Breysacher, Pierre Laurent-Puig, Laurent Mineur, Guillaume Roquin, Anthony Lopez, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Hôpital privé Jean Mermoz, Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Sainte Catherine [Avignon], Hôpital Louis Pasteur [Colmar] (CH Colmar), Servier, Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Oncology, medicine.medical_specialty, Esophageal Neoplasms, Paclitaxel, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Esophageal cancer, Phases of clinical research, Irinotecan, 03 medical and health sciences, chemistry.chemical_compound, Clinical Trials, Phase II as Topic, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Multicenter Studies as Topic, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, 030304 developmental biology, Cisplatin, 0303 health sciences, Chemotherapy, Hepatology, Performance status, business.industry, Gastroenterology, medicine.disease, 3. Good health, Survival Rate, chemistry, Docetaxel, 030220 oncology & carcinogenesis, Disease Progression, Quality of Life, Squamous cell cancer, Esophageal Squamous Cell Carcinoma, Fluorouracil, France, Neoplasm Recurrence, Local, business, medicine.drug
Abstract

Half of patients newly diagnosed with esophageal squamous cell cancer (ESCC) have metastatic disease (mESCC) and therefore a poor prognosis. Furthermore, half of patients with initial loco-regional disease present disease recurrence after surgery and/or chemoradiation. In mESCC, the recommended first-line treatment combines 5-fluorouracil and cisplatin, although this has not been validated by a phase III trial. Patients with disease progression or recurrence after platinum-based chemotherapy and good performance status probably benefit from second-line chemotherapy. Several molecules have been evaluated in phase I/II trials or retrospective studies (docetaxel, paclitaxel and irinotecan) but no randomised studies are available. OESIRI is a multicentre, randomised, open-label phase II trial designed to evaluate efficacy and safety of liposomal irinotecan (nal-IRI) plus 5-FU versus paclitaxel as second-line therapy in patients with mESCC. The main inclusion criteria are histologically proven mESCC in progression after first-line platinum-based chemotherapy. Patients with initial resectable disease can be included if recurrence occurred within 6 months. The primary objective is to evaluate the percentage of patients alive 9 months after randomisation. Secondary endpoints are progression-free survival, overall survival, response rate, safety and quality of life. In addition, circulating tumour DNA will be monitored to assess its prognostic value.

Published
2020

3. Predictive factors for early progression during induction chemotherapy and chemotherapy-free interval: analysis from PRODIGE 9 trial

Author

Jean-Marc Phelip, Valérie Boige, Karine Le Malicot, Julien Taieb, Jean-Marc Gornet, Jaafar Bennouna, Olivier Bouché, Eric Francois, for Prodige investigators, Veronique Guerin-Meyer, Oana Cojocarasu, Marie-Christine Kaminsky, Joëlle Egreteau, Laetitia Dahan, Jean-Baptiste Bachet, François Ghiringhelli, Roger Faroux, Mohamed Gasmi, Thomas Aparicio, Christian Borel, and Côme Lepage

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Multivariate analysis, Colorectal cancer, medicine.medical_treatment, Logistic regression, Article, law.invention, Free interval, Prognostic markers, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Aged, 030304 developmental biology, 0303 health sciences, Chemotherapy, business.industry, Induction chemotherapy, Induction Chemotherapy, medicine.disease, Clinical trial, 030220 oncology & carcinogenesis, Disease Progression, Female, Colorectal Neoplasms, business
Abstract

Background Identifying patients with metastatic colorectal cancer who will have an early disease progression during induction chemotherapy (IC) and identifying patients who may have a chemotherapy-free interval (CFI) after IC are two major challenges. Methods A logistic model was used to identify factors associated with early progression during IC and with short duration of the first CFI in 488 patients enrolled in the PRODIGE 9 trial. Independent factors were defined with a threshold 0.10. Results In multivariate analysis, baseline leukocytes >10 × 109/L (OR = 1.98 [1.02–3.8], p = 0.04), and stable or increasing CEA at 2 months (OR = 3.61 [1.68–7.75], p = 0.01) were independent factors associated with progression during IC. Male gender (OR = 1.725 [0.92–3.325], p = 0.09) and no tumour response at first evaluation (OR = 1.90 [0.96–3.76], p = 0.07) were significantly associated with a short CFI. The presence of BRAF V600E mutation was also associated with short CFI (OR = 4.59 [0.95; 22.3], p = 0.058). Conclusion High baseline leukocyte count and the lack of CEA decrease level at first evaluation were associated with early progression, and could be in favour of early chemotherapy intensification. Male gender, no tumour response at first evaluation and BRAF mutation are associated with a short CFI, and may be considered for maintenance chemotherapy after IC. Clinical trial number NCT00952029.

Published
2020

4. First-line chemotherapy with raltitrexed in metastatic colorectal cancer: an Association des Gastro-entérologues Oncologues (AGEO) multicentre study

Author

Christophe Locher, Emilie Hafliger, Anna Pellat, Roger Faroux, Claire Gallois, Julien Taieb, Edouard Auclin, A. Perret, Vincent Hautefeuille, Violaine Randrian, Anthony Turpin, Simon Pernot, Lola-Jade Palmieri, Olivier Dubreuil, Debora Basile, Clélia Coutzac, Marie Dior, and Pascal Artru

Subjects
Oncology, medicine.medical_specialty, Bevacizumab, Survival, Colorectal cancer, medicine.medical_treatment, Thiophenes, Raltitrexed, Internal medicine, Chemotherapy toxicity, Metastatic colorectal cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Contraindication, Retrospective Studies, Chemotherapy, Hepatology, business.industry, Rectal Neoplasms, Gastroenterology, medicine.disease, Chemotherapy regimen, digestive system diseases, Oxaliplatin, Irinotecan, Colonic Neoplasms, Quinazolines, business, Colorectal Neoplasms, medicine.drug
Abstract

Background In case of contraindication or intolerance to fluoropyrimidines, raltitrexed is a validated alternative in metastatic colorectal cancer (mCRC), associated or not with oxaliplatin. Little is known about the outcomes of raltitrexed combined with irinotecan or targeted therapies. Methods This retrospective multicentre study enroled mCRC patients treated with first-line raltitrexed-based chemotherapy. Treatment-related toxicities were recorded. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start. Results 75 patients were treated with raltitrexed alone, TOMOX, or TOMIRI with or without bevacizumab. Grade 3–4 adverse events were seen in 31% of patients, without significant difference between the different treatment schedules. amongst the 36 patients with a history of fluoropyrimidine-induced cardiac toxicity, none developed cardiovascular events on raltitrexed. Median PFS and OS were 10.6 (95% CI 8.2 – 13.1) and 27.4 months (95% CI 24.1–38.1), respectively. Considering the chemotherapy regimen, TOMOX was significantly associated with better PFS and OS compared to TOMIRI and raltitrexed alone. Conclusions In patients with mCRC not eligible for fluoropyrimidines, first-line raltitrexed-based chemotherapy had an acceptable safety profile. PFS and OS were consistent with usual survival data in mCRC, and significantly better in patients treated with TOMOX, independently of associated targeted therapies.

Published
2021

5. Evaluation of two nutritional scores' association with systemic treatment toxicity and survival in metastatic colorectal cancer: an AGEO prospective multicentre study

Author

Julien Taieb, Edouard Auclin, Yosra Zaimi, Maximilien Barret, Claire Gallois, Simon Pernot, Roger Faroux, Christophe Locher, Pascal Artru, Astrid Lièvre, Thierry Lecomte, Lysiane Marthey, Cancer Research and Personalized Medicine - CARPEM [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Eugène Marquis (CRLCC), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital privé Jean Mermoz [Lyon], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Francois Rabelais [Tours], Centre Hospitalier de Meaux, AP-HP - Hôpital Antoine Béclère [Clamart], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), and CCSD, Accord Elsevier

Subjects
Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Multivariate analysis, Drug-Related Side Effects and Adverse Reactions, Colorectal cancer, [SDV]Life Sciences [q-bio], Nutritional Status, Kaplan-Meier Estimate, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Prospective Studies, Neoplasm Metastasis, Prospective cohort study, Adverse effect, Chemotherapy toxicity, Aged, 2. Zero hunger, Metastatic colorectal cancer, business.industry, Malnutrition, Hazard ratio, Cancer, Odds ratio, Middle Aged, Prognosis, medicine.disease, Confidence interval, 3. Good health, [SDV] Life Sciences [q-bio], Nutrition Assessment, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Multivariate Analysis, NRI, PG-SGA, Female, Colorectal Neoplasms, business
Abstract

Introduction The Patient-Generated Subjective Global Assessment (PG-SGA) is currently the standard nutritional assessment tool for patients with cancer. In a retrospective assessment of a prospective cohort, we showed that the Nutritional Risk Index (NRI) seemed to be associated with treatment toxicity and survival in patients with metastatic colorectal cancer (mCRC). Objective The objective of this study was to compare these two nutritional tools (PG-SGA and NRI) on their correlation with chemotherapy-related toxicity and survival in non–pre-treated patients with mCRC. Methods This prospective multicentre observational study enrolled non–pre-treated patients with mCRC. PG-SGA and NRI were performed at the onset of first-line chemotherapy. Treatment-related toxicities were registered according to National Cancer Institute Common Toxicity Criteria Adverse Event version 4.0. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment. Results A total of 168 patients were included from eight French centres. Patients were considered malnourished in 41% of cases according to PG-SGA and 56% of cases according to the NRI. In multivariate analysis, malnutrition according to PG-SGA was significantly associated with chemotherapy-related grade ≥2 clinical toxicities (odds ratio: 3.7; 95% confidence interval [CI]: 1.7–8.4; p = 0.001) and OS (hazard ratio [HR]: 2.6; 95% CI: 1.3–5.3; p = 0.006), but not with PFS (HR: 1.5; 95% CI: 0.8–2.6; p = 0.2). Conversely, malnutrition according to the NRI was not significantly associated with these tolerance and efficacy parameters. Conclusion Although more complex to perform in daily oncology practice, the PG-SGA score appears to be the best nutritional assessment tool because of its strong association with clinically relevant oncological outcomes such as OS and treatment-related toxicities in patients with mCRC.

Published
2019

6. Intérêts et limites de la recherche du déficit en dihydropyrimidine déshydrogénase dans le suivi des patients traités par fluoropyrimidines : résultats de deux enquêtes nationales de pratiques réalisées auprès des médecins et des biologistes

Author

Olivier Bouché, Marie-Christine Etienne-Grimaldi, Karine Le Malicot, Jean-Christophe Boyer, Jean-François Seitz, Joseph Ciccolini, Jean-Louis Legoux, Thierry André, Marie-Anne Loriot, Chantal Barin-Le-Guellec, Joël Guigay, Pierre Michel, Fabienne Thomas, David Malka, Paolo Carni, Juliette Thariat, Fadil Masskouri, Roger Faroux, and Suzette Delaloge

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, business.industry, French, Hematology, General Medicine, language.human_language, 3. Good health, 03 medical and health sciences, Health insurance system, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Family medicine, language, Medicine, Radiology, Nuclear Medicine and imaging, National level, business, Reimbursement
Abstract

Dihydropyrimidine dehydrogenase (DPD) deficiency is the main cause of early severe toxicities induced by fluoropyrimidines (FP). The French Group of Clinical Oncopharmacology (GPCO)-Unicancer and the French Pharmacogenetics Network (RNPGx) initiated two surveys, one addressed to oncologists, the other to biologists, in order to evaluate routine practices regarding DPD deficiency screening at national level, as well as compliance, motivations and obstacles for implementation of these tests. These anonymized online surveys were performed with the logistic assistance of the Francophone Federation of Digestive Oncology (FFCD) and the support of numerous medical and biological societies. The surveys were conducted in 2016-2017 before the creation of the French INCa/HAS expert panel, which contributed to the drafting of rules and recommendations for DPD deficiency screening published in December 2018. In all, 554 questionnaires from clinicians were analyzed (23% participation) and 35 from biologists. The main arguments raised by clinicians for justifying the limited practice of DPD deficiency screening were: the lack of recommendations from medical societies or Health Authorities, delays in obtaining results, and the lack of adequate reimbursement by the health insurance system. The goal of these surveys was to provide the French Health Authorities with an overview on nationwide DPD-deficiency screening practices and thus help to design recommendations for the standardization and improvement of the management and safety of cancer patients receiving FP-based chemotherapy.

Published
2019

7. Carcinoembryonic Antigen Levels and Survival in Stage III Colon Cancer: Post hoc Analysis of the MOSAIC and PETACC-8 Trials

Author

Josep Tabernero, Edouard Auclin, Roger Faroux, Christophe Louvet, Aimery de Gramont, Jean-Luc Van Laethem, Côme Lepage, Maria Banzi, Magdalena Benetkiewicz, Gunnar Folprecht, Ramon Salazar, Thierry André, Julien Taieb, Thomas Aparicio, Enrico Mini, Dewi Vernerey, and Tamas Hickish

Subjects
0301 basic medicine, medicine.medical_specialty, Epidemiology, Population, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Risk groups, Internal medicine, Post-hoc analysis, Medicine, education, neoplasms, Survival analysis, education.field_of_study, biology, business.industry, digestive system diseases, Stage III Colon Cancer, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, Restricted cubic splines, biology.protein, business
Abstract

Background: We explored and validated the association of postoperative carcinoembryonic antigen (CEA) with disease-free survival (DFS) and overall survival (OS) in stage III colon cancer. Methods: Patients with stage III colon cancer from the MOSAIC and PETACC-8 trials were enrolled. The relation between CEA and outcomes was continuously modeled with the restricted cubic splines (RCS) method. Association of CEA with outcomes was assessed by the Kaplan–Meier method, with two risk groups among patients with a CEA level ≤5 ng/mL. Multivariate Cox proportional hazard models were constructed. Results: The CEA level was available in 1,292 (96%) and 2,477 (97%) patients in the discovery and validation cohorts. The RCS analysis confirmed that patients with a CEA level >5 ng/mL were at highest risk of recurrence or death and those with a CEA level ≤5 ng/mL presented a heterogeneous risk population. In the discovery cohort, the 3-year DFS rate was 75%, 65%, and 45% in a group of patients with CEA level of 0–1.30 ng/mL (n = 630), 1.30–5 ng/mL (n = 613), and >5 ng/mL (n = 49), respectively (P < 0.001). CEA was independently associated with endpoints. All findings were confirmed in the validation cohort. Conclusions: Postoperative CEA level was highly and independently associated with DFS and OS, especially in patients with a CEA level of ≤5 ng/mL, suggesting that this cutoff is not optimal. Impact: CEA levels should be applied more accurately in future trials and clinical practice.

Published
2019

8. Increased incidence of Campylobacter enteritis and their quinolone resistance between 2010 and 2015: Results of a French national observatory conducted in 21 general hospitals (CHG)

Author

Maria Ortiz Correro, Roger Faroux, Charlotte Pujol, Audrey Jeanne, Georges Barjonet, Laura Le Guilloux, Patrick Marthelet, Ratmutcho Arotcarena, Pierre Lahmek, Christophe Locher, Christophe Renou, Aude Grébert Manuardi, Claire Charpignon, Laurent Villeneuve, Thierry Paupard, Stéphane Bland, Christian Cattoen, Jacques Vaucel, Pascal Pouedras, Laurent Souply, Valérie Desroys, Lydie Libier, Xavier Causse, Vincent Quentin, Caroline Joubrel-Guyot, Arnaud Boruchowicz, Ahmed Tsouria, Hélène Garrec, Annick Verhaeghe, Frédéric Heluwaert, Bernard Denis, Marie Trompette, Mahjoub Rahma, Jenny Gallou, Bertrand Condat, Gilles Macaigne, Jean-Louis Payen, Stéphane Nahon, Meddi Kaassi, Anne-Lise Toyer, Pauline Touroult-Jupin, Magali Picon, Denis Grasset, and Didier Poisson

Subjects
Adult, medicine.medical_specialty, Salmonella, Adolescent, Prevalence, Drug resistance, Hospitals, General, medicine.disease_cause, Enteritis, Young Adult, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, Internal medicine, Campylobacter Infections, Drug Resistance, Bacterial, Epidemiology, medicine, Humans, Aged, Retrospective Studies, Aged, 80 and over, Hepatology, business.industry, Incidence, Campylobacter, Incidence (epidemiology), Gastroenterology, Middle Aged, medicine.disease, Campylobacter enteritis, 030220 oncology & carcinogenesis, Salmonella Infections, 030211 gastroenterology & hepatology, France, Seasons, business
Abstract

In Europe, the number of cases of Campylobacter enteritis and their quinolone resistance is increasing. The aims of this work were to evaluate: (1) the hospital epidemiology of bacterial enteritis between 2010 and 2015. (2) The proportion of Campylobacter and Salmonella enteritis. (3) Resistance to quinolones in adult and paediatric populations. (4) To investigate possible regional epidemiological and bacteriological disparities.This is a multicentric study carried out in 21 general hospitals (CHG) representing 14 French regions with a prospective collection of the results of coprocultures from 2010 to 2015 in adult and paediatric populations (children 15 years old not exposed to quinolones). The epidemiological and bacteriological data were collected from software laboratory for positive stool cultures for Campylobacter and Salmonella. The results were compared year by year and by a period of 2 years.In adults, Campylobacter enteritis was each year significantly more frequent than Salmonella (P 0.001), with a significant increase from 2010 to 2015 (P 0.05). In children, there was also a significant and stable predominance of Campylobacter enteritis over the study period (P = 0.002). The quinolone resistance of Campylobacter was greater than 50% on the whole territory, with no North-South difference over the three periods studied. It increased significantly from 2012 to 2015 in adults (48% to 55%, P 0.05) and in children (54% to 61%, P = 0.04).Our results confirm the increase in the prevalence of Campylobacter enteritis compared to Salmonella between 2010 and 2015. The quinolone resistance of Campylobacter is greater than 50% on the whole territory, stable between 2010 and 2015 in adults and significantly increased in children.

Published
2019

9. Early evaluation using a radiomic signature of unresectable hepatic metastases to predict outcome in patients with colorectal cancer treated with FOLFIRI and bevacizumab

Author

Anthony, Dohan, Benoit, Gallix, Boris, Guiu, Karine, Le Malicot, Caroline, Reinhold, Philippe, Soyer, Jaafar, Bennouna, Francois, Ghiringhelli, Emilie, Barbier, Valérie, Boige, Julien, Taieb, Olivier, Bouché, Eric, François, Jean-Marc, Phelip, Christian, Borel, Roger, Faroux, Jean-Francois, Seitz, Stéphane, Jacquot, Meher, Ben Abdelghani, Faiza, Khemissa-Akouz, Dominique, Genet, Jean Louis, Jouve, Yves, Rinaldi, Françoise, Desseigne, Patrick, Texereau, Etienne, Suc, Come, Lepage, Thomas, Aparicio, Christine, Hoeffel, Zied, Ladhib, Service de Radiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), McGill University Health Center [Montreal] (MUHC), l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), CHU Strasbourg, Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Equipe EPICAD (LNC - U1231), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut Gustave Roussy (IGR), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Paul Strauss, CRLCC Paul Strauss, Service de chirurgie digestive (CH de La Roche-sur-Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Cancérologie du Grand Montpellier (CCGM), Centre Hospitalier Saint Jean de Perpignan, Polyclinique de Limoges - site François Chénieux [Limoges], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Léon Bérard [Lyon], CHU Mont de Marsan, Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Université de Reims Champagne-Ardenne (URCA), and Hôpital Maison Blanche

Subjects
Male, Oncology, Colorectal cancer, medicine.medical_treatment, Leucovorin, Kaplan-Meier Estimate, 030218 nuclear medicine & medical imaging, MESH: Camptothecin / administration & dosage, Camptothecin / analogs & derivatives, Colorectal Neoplasms / drug therapy, Colorectal Neoplasms / pathology, Computational Biology, Female, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Prospective cohort study, Aged, 80 and over, Liver Neoplasms, Gastroenterology, MESH: Radiographic Image Interpretation, Computer-Assisted, Response Evaluation Criteria in Solid Tumors, Survival Rate, Tomography, X-Ray Computed, Middle Aged, Bevacizumab, 030220 oncology & carcinogenesis, Cohort, FOLFIRI, Radiographic Image Interpretation, Computer-Assisted, Fluorouracil, Colorectal Neoplasms, Clinical decision making, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Fluorouracil / administration & dosage, Humans, Leucovorin / administration & dosage, Liver Neoplasms / diagnostic imaging, Computerised image analysis, 03 medical and health sciences, Colorectal metastases, MESH: Adult, Antineoplastic Combined Chemotherapy Protocols / administration & dosage, Bevacizumab / administration & dosage, Camptothecin / administration & dosage, Predictive Value of Tests, Internal medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Chemotherapy, MESH: Liver Neoplasms / secondary, Aged, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Log-rank test, Irinotecan, Camptothecin, business
Abstract

PurposeThe objective of this study was to build and validate a radiomic signature to predict early a poor outcome using baseline and 2-month evaluation CT and to compare it to the RECIST1·1 and morphological criteria defined by changes in homogeneity and borders.MethodsThis study is an ancillary study from the PRODIGE-9 multicentre prospective study for which 491 patients with metastatic colorectal cancer (mCRC) treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab had been analysed. In 230 patients, computed texture analysis was performed on the dominant liver lesion (DLL) at baseline and 2 months after chemotherapy. RECIST1·1 evaluation was performed at 6 months. A radiomic signature (Survival PrEdiction in patients treated by FOLFIRI and bevacizumab for mCRC using contrast-enhanced CT TextuRe Analysis (SPECTRA) Score) combining the significant predictive features was built using multivariable Cox analysis in 120 patients, then locked, and validated in 110 patients. Overall survival (OS) was estimated with the Kaplan-Meier method and compared between groups with the logrank test. An external validation was performed in another cohort of 40 patients from the PRODIGE 20 Trial.ResultsIn the training cohort, the significant predictive features for OS were: decrease in sum of the target liver lesions (STL), (adjusted hasard-ratio(aHR)=13·7, p=1·93×10–7), decrease in kurtosis (ssf=4) (aHR=1·08, p=0·001) and high baseline density of DLL, (aHR=0·98, p0·02 had a lower OS in the training cohort (pConclusionA radiomic signature (combining decrease in STL, density and computed texture analysis of the DLL) at baseline and 2-month CT was able to predict OS, and identify good responders better than RECIST1.1 criteria in patients with mCRC treated by FOLFIRI and bevacizumab as a first-line treatment. This tool should now be validated by further prospective studies.Trial registrationClinicaltrial.gov identifier of the PRODIGE 9 study: NCT00952029.Clinicaltrial.gov identifier of the PRODIGE 20 study: NCT01900717.

Published
2019

10. PREMIUM: A French prospective multicenter observational study of factors impacting on efficacy and compliance to cetuximab treatment in first-line KRAS wild-type metastatic colorectal cancer

Author

A. Abakar Mahamat, N. Mathé, Roger Faroux, R. Boustany, P. Soulié, L. Moreau, Isabelle Baumgaertner, R. Hervé, J. M. Phelip, D. Smith, J. M. Bons, L. Vazquez, Laurent Miglianico, Eric Francois, Rosine Guimbaud, Laurent Mineur, Louis-Marie Dourthe, A. L. Villing, S. Remy, E. Achille, N. Bonichon, Carine Plassot, and I. Rabbia

Subjects
0301 basic medicine, Oncology, Male, Colorectal cancer, Cancer Treatment, ECOG Performance Status, Cetuximab, medicine.disease_cause, Toxicology, Pathology and Laboratory Medicine, Metastasis, 0302 clinical medicine, Antineoplastic Agents, Immunological, Basic Cancer Research, Medicine and Health Sciences, Neoplasm Metastasis, Paronychia, Aged, 80 and over, Univariate analysis, Multidisciplinary, Hazard ratio, Smoking, Middle Aged, Tumor Resection, Primary tumor, Surgical Oncology, Treatment Outcome, 030220 oncology & carcinogenesis, Medicine, Female, KRAS, Colorectal Neoplasms, medicine.drug, Research Article, Compliance, Clinical Oncology, Adult, medicine.medical_specialty, Science, Surgical and Invasive Medical Procedures, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Malignant Tumors, Internal medicine, medicine, Humans, neoplasms, Aged, Colorectal Cancer, Folliculitis, Toxicity, Surgical Resection, business.industry, Proportional hazards model, Cancers and Neoplasms, Biology and Life Sciences, medicine.disease, digestive system diseases, 030104 developmental biology, Clinical Medicine, business
Abstract

Background Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC. Patients and methods PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety. Results A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6–12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies. Conclusions ECOG PS

Published
2020

11. Skeletal muscle loss during chemotherapy and its association with survival and systemic treatment toxicity in metastatic colorectal cancer: An AGEO prospective multicenter study

Author

Julien Taieb, Camille Bourillon, Maximilien Barret, Claire Gallois, Lysiane Marthey, Roger Faroux, Pascal Artru, Edouard Auclin, Thierry Lecomte, Astrid Lièvre, Simon Pernot, Christophe Locher, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Groupe Hospitalier Diaconesses Croix Saint-Simon, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Meaux, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Université de Rennes (UR), and Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée)

Subjects
medicine.medical_specialty, Sarcopenia, Colorectal cancer, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Antineoplastic Agents, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Humans, Hypoalbuminemia, Prospective Studies, education, Muscle, Skeletal, Chemotherapy toxicity, 2. Zero hunger, education.field_of_study, Chemotherapy, Skeletal muscle index, Hepatology, business.industry, Metastatic colorectal cancer, Skeletal muscle, medicine.disease, Prognosis, Survival Analysis, 3. Good health, medicine.anatomical_structure, Treatment Outcome, 030220 oncology & carcinogenesis, Toxicity, 030211 gastroenterology & hepatology, Observational study, PG-SGA, business, Colorectal Neoplasms
Abstract

International audience; Purpose: We showed in a previous study that the PG-SGA score is associated with survival and chemotherapy-related toxicities in metastatic colorectal cancer (mCRC) patients. The objective was to evaluate the association between pretherapeutic sarcopenia and variation in skeletal muscle index (SMI) during treatment with these outcomes in the same population. Methods: This prospective, multicenter, observational study enrolled non-pretreated mCRC patients. SMI was measured on routine CT scan at day 0 (D0) and day 60 (D60). Nutritional factors were collected at D0. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start. Results: 149 patients were included from 7/2013 to 11/2016. Pretherapeutic sarcopenia was not significantly associated with survival or chemotherapy-related toxicities. The decrease in SMI > 14% was significantly associated with shorter PFS (6 vs 9 mo; HR 1.8, 95% CI 1.1−3.1, p = 0.02) and OS (8.5 vs 26 mo; HR 2.6, 95% CI 1.4−4.8, p = 0.002), independently of hypoalbuminemia and malnutrition defined by PG-SGA. Patients with a SMI decrease > 14% had a higher rate of grade ≥ 2 clinical toxicities (40% vs 22%, OR 3.0, 95% CI 1.2−7.7, p = 0.02), but the difference was not statistically significant in multivariable analysis. Conclusion: To our knowledge, this is the first study to assess prospectively the association of skeletal muscle loss with survival and treatment toxicities in non-pretreated patients with mCRC. Pretherapeutic sarcopenia was not associated with poor outcomes, but the loss of skeletal muscle mass within 60 days from treatment start was highly prognostic, independently of other prognostic and nutritional factors. © 2020 Elsevier Masson SAS

Published
2020

12. Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study

Author

Julien Taieb, Jean-François Emile, Pierre Laurent-Puig, Magali Svrcek, Dewi Vernerey, Amos Kirilovsky, R. Ben Jannet, Alex Duval, Thierry André, Roger Faroux, Julie Henriques, Jaafar Bennouna, Florence Marliot, Laurent Mineur, Jérôme Galon, Christophe Borg, Franck Pagès, Aurelie Catteau, Jérôme Desramé, Christophe Louvet, Fabienne Hermitte, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Institut Mutualiste de Montsouris (IMM), Institut Sainte Catherine [Avignon], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital privé Jean Mermoz, Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), CHD Vendee (La Roche Sur Yon), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Instabilité des microsatellites et cancers [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Institut National Du Cancer, INCa: 2012-218 Institut National de la Santé et de la Recherche Médicale, Inserm Ligue Contre le Cancer: AOM09 202 Université Paris Descartes Institut National de la Santé et de la Recherche Médicale, Inserm, This work was supported by the National Institute of Health and Medical Research (INSERM), AP-HP , University Paris Descartes , the Cancéropole Ile-de-France , the Cancer Research for Personalized Medicine (CARPEM), Paris Alliance of Cancer Research Institutes (PACRI), the LabEx Immuno-oncology , [no grant number] the National Cancer Institute of France (INCa, and ref 2012-218), La Ligue Contre le Cancer , the French Ministry of Health Program Hospitalier de Recherche Clinique 2009 (PHRC 2009) [grant number AOM09 202 ] for the IDEA clinical trial, and HalioDx for Immunoscore®.

Subjects
0301 basic medicine, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, Immunoscore, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemotherapy, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Adjuvant therapy, Medicine, Humans, Prospective Studies, predictive, Neoplasm Staging, Duration of Therapy, business.industry, Proportional hazards model, Hazard ratio, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hematology, medicine.disease, Prognosis, Confidence interval, 3. Good health, Oxaliplatin, 030104 developmental biology, Oncology, colon cancer, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Cohort, Colonic Neoplasms, biomarker, Fluorouracil, France, business, prognostic, Cohort study, medicine.drug
Abstract

International audience; Background: The Immunoscore (IS), which prognostically classifies stage I–III colon cancer (CC) patients, was evaluated in the International Duration Evaluation of Adjuvant Therapy (IDEA) France cohort study investigating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in stage III CC patients.Patients and methods: Densities of CD3+ and CD8+ T cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS. Mismatch repair status was determined by immunohistochemistry or by pentaplex PCR. Prediction of disease-free survival (DFS) by IS was analyzed by a multivariable Cox regression model in each study arm. Harrell's C-statistics were used to investigate the IS performance.Results: Samples of 1322 patients were available. IS Low, Intermediate (Int), and High were observed in 43.6%, 47.0%, and 9.4% of patients, respectively. IS Low identified patients at higher risk of relapse or death compared with Int + High [hazard ratio (HR) = 1.54; 95% confidence interval (CI) 1.24–1.93, P = 0.0001]. The 3-year DFS was 66.80% (95% CI 62.23–70.94) for IS Low and 77.14% (95% CI 73.50–80.35) for IS Int + High. In multivariable analysis, IS remained significantly independently associated with DFS (P = 0.003) when adjusted for sex, histological grade, T/N stage, and microsatellite instability. For mFOLFOX6-treated patients (91.6% of the cohort), a statistical significant interaction was observed for the predictive value of IS for treatment duration (3 versus 6 months) in terms of DFS (P = 0.057). IS Int + High significantly predicted benefit of 6 months of treatment (HR = 0.53; 95% CI 0.37–0.75; P = 0.0004), including clinically low- and high-risk stage III CC (all P < 0.001). Conversely, patients with IS Low (46.4%) did not significantly benefit from the 6-month mFOLFOX6 versus the 3-month mFOLFOX6.Conclusions: The prognostic value of IS for DFS was confirmed in patients with stage III CC treated with oxaliplatin-based chemotherapy. Its predictive value for DFS benefit of longer duration of mFOLFOX6 adjuvant treatment was found in IS Int + High. These results will be validated in an external independent cohort. ClinicalTrials.gov registration: NCT03422601; EudraCT Number: 2009-010384-16.

Published
2020

13. Erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial

Author

Olivier Bouché, Iman El Hariry, Thierry Lecomte, Thierry André, David Tougeron, Jérôme Cros, Adam Hamm, Jean-Baptiste Bachet, Jean-Philippe Metges, Christine Rebischung, Pascal Hammel, Laurent Mineur, Christophe Tournigand, Christophe Louvet, Farid El Hajbi, Portales Fabienne, Richard Kay, Rosine Guimbaud, Anu Gupta, Roger Faroux, Christelle De La Fouchardiere, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Sainte Catherine [Avignon], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre Léon Bérard [Lyon], Service d'Oncologie Médicale [Montsouris], Institut Mutualiste de Montsouris (IMM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Service de chirurgie digestive (CH de La Roche-sur-Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Service de gastroentérologie et cancérologie digestive [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint-Antoine [APHP], CRLCC Oscar Lambret, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, Cancer Research, Organoplatinum Compounds, Survival, medicine.medical_treatment, Biopsy, Leucovorin, Kaplan-Meier Estimate, Gastroenterology, Deoxycytidine, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Aged, 80 and over, 0303 health sciences, Middle Aged, Progression-Free Survival, 3. Good health, Erythrocyte, Oncology, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor, Fluorouracil, medicine.drug, Adult, Asparaginase, medicine.medical_specialty, Neutropenia, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Pancreatic cancer, Internal medicine, medicine, Humans, Adverse effect, Pancreas, Response Evaluation Criteria in Solid Tumors, 030304 developmental biology, Aged, Neoplasm Staging, Chemotherapy, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Gemcitabine, PHASE IIB TRIAL, Pancreatic Neoplasms, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, Pancreatic adenocarcinoma, Follow-Up Studies, Asparagine synthetase
Abstract

International audience; PURPOSE: This Phase IIb (NCT02195180) open-label study evaluated erythrocyte-encapsulated asparaginase (eryaspase) in combination with chemotherapy in second-line advanced pancreatic adenocarcinoma.METHODS: Eligible patients were randomized 2:1 to either eryaspase in combination with gemcitabine or mFOLFOX6 (eryaspase arm), or to gemcitabine or mFOLFOX6 alone (control arm). Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients with low asparagine synthetase (ASNS) expression. Secondary endpoints included OS and PFS in the entire population.RESULTS: 141 patients were randomized (eryaspase arm, n = 95; control arm, n = 46). Median OS and PFS in patients with low ASNS expression were 6.2 months (95% CI, 5.1-8.8) in the eryaspase arm versus 4.9 months (3.1-7.1) in the control arm (HR, 0.63; 95% CI, 0.39-1.01; P = 0.056) and 2.0 months (95% CI, 1.8-3.4) in the eryaspase arm versus 1.8 months (1.4-3.8) in the control arm (HR, 0.67; 95% CI, 0.40-1.12; P = 0.127), respectively. In the entire population, median OS and PFS for the eryaspase arm versus control were 6.0 months versus 4.4 months (HR, 0.60; P = 0.008) and 2.0 months versus 1.6 months (HR, 0.56; 95% CI, 0.37-0.84; P = 0.005), respectively. The combination of eryaspase and chemotherapy was well tolerated. The most frequent Grade 3/4 adverse events in the eryaspase arm (n = 93) were gamma-glutamyltransferase increase (16 [17.2%]), neutropenia (12 [12.9%]), and physical health deterioration (12 [12.9%]).CONCLUSION: Eryaspase in combination with chemotherapy is associated with improvements in OS and PFS, irrespective of ASNS expression in second-line advanced pancreatic adenocarcinoma. A Phase III trial is underway.

Published
2020

14. LBA57 Unicancer PRODIGE 24/CCTG PA6 trial: Updated results of a multicenter international randomized phase III trial of adjuvant mFOLFIRINOX (mFFX) versus gemcitabine (gem) in patients (pts) with resected pancreatic ductal adenocarcinomas (PDAC)

Author

A. Lambert, E. Francois, Anthony Turpin, L. Monard, Marc Ychou, James Joseph Biagi, Thierry Lecomte, A. Lopez, Roger Faroux, Alice C. Wei, J-B. Bachet, Florence Castan, C. Belletier, Patrick Rat, O. Bouche, Pascal Hammel, Eric Assenat, T. Conroy, Pascal Artru, and Emmanuel Mitry

Subjects
Oncology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Hematology, Gemcitabine, Internal medicine, Medicine, In patient, Pancreatic carcinoma, business, Adjuvant, medicine.drug
Published
2021

15. Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: Assessment of a multiparametric approach

Author

Ludovic Rosenfeld, Virginie Berger, Erick Gamelin, Karine Bouhier-Leporrier, Claire Stampfli, Isabelle Baumgaertner, Thierry Lecompte, Mehdi Kaassis, Eric Francois, Christophe Borg, Alain Morel, Celia Roemer-Becuwe, Veronique Guerin-Meyer, Roger Faroux, Michèle Boisdron-Celle, Oana Cojocarasu, Jean Philippe Metges, Olivier Capitain, Marie Pierre Galais, and Jaafar Bennouna

Subjects
0301 basic medicine, Chemotherapy, medicine.medical_specialty, business.industry, Colorectal cancer, medicine.medical_treatment, Incidence (epidemiology), Hematology, medicine.disease, Gastroenterology, Surgery, 03 medical and health sciences, Dihydropyrimidine dehydrogenase deficiency, 030104 developmental biology, 0302 clinical medicine, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, Internal medicine, Toxicity, medicine, Dihydropyrimidine dehydrogenase, Prospective cohort study, business, medicine.drug
Abstract

5-Fluorouracil (5-FU)–based treatments can lead to early-onset severe (4%–5%) even fatal (0.3%) toxicities in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. This multicenter prospective cohort study aimed to assess the clinical benefit of pretherapeutic screening for DPD deficiency using a multiparametric approach. Two parallel cohorts of patients treated with 5-FU–based chemotherapy for colorectal carcinoma were compared in a prospective nonrandomized study. In arm A, patients had DPD deficiency screening before treatment, whereas in arm B no pretherapy screening was performed. Dosing was based on 5-FU administration guidelines of each institution. DPD deficiency screening was performed using a combined multiparametric approach (5-FUODPM Tox). The frequency of early grade 4–5 toxic events potentially induced by 5-FU was compared in the two groups. At total of 1,142 patients (n = 1,116 evaluable) were enrolled. In arm A, out of 718 evaluable patients, nine grade 4 early toxicities potentially related to 5-FU were reported in nine patients (1.2%) with no toxic death despite one complete DPD deficiency and 24 partial deficiencies. The 24 patients with partial deficiency had safe pharmacokinetics (PK)-monitored 5-FU. In arm B, among 398 evaluable patients, 17 grade 4–5 toxic early events potentially related to 5-FU were reported in 12 patients (4.2%). The incidence of early severe toxicity was significantly higher in arm B (P = .0019), confirming the positive impact of pretherapeutic DPD assessment. The percent of patients with a toxicity grade 3 or higher observed in arm A was 10.8% (n = 78) compared to 17.55% (n = 69) in arm B (P = .0497). The percentage of death was reduced from 2.5/1,000 in arm B to 0 in arm A. The time to occurrence of all grade ≥3 toxicities was determined in both arms and the difference between the two arms was significant (P = .047). Overall, one patient with complete DPD deficiency confirmed retrospectively died within 13 days from grade 5 multivisceral toxicity. Enrollment was prematurely closed after external experts’ decision. In conclusion, multiparametric pretherapeutic DPD deficiency screening significantly lowered the risk of early severe toxicity and avoided an early toxic death. This approach should be used for safe administration of 5-FU–based treatments.

Published
2017

16. Middle‐term mortality and re‐bleeding after initial diverticular bleeding: A nationwide study of 365 mostly elderly French patients

Author

Andre-Jean Remy, Pierre Lahmek, F. Bourhis, René Piperaud, Denis Grasset, B. Bour, Jean-Pierre Arpurt, Stéphane Nahon, Gilbert Bordes, Jacques-Arnaud Seyrig, Bruno Lesgourgues, Claire Gallois, Claire Charpignon, Alexandre Pariente, Gilles Macaigne, Eric Poncin, Roger Faroux, Frédéric Heluwaert, David Bernardini, J. Henrion, Diane Lorenzo, Christine Champion, Chantal Naouri, Magali Picon, and Guy Bellaiche

Subjects
medicine.medical_specialty, Gastrointestinal bleeding, Pediatrics, business.industry, Mortality rate, Gastroenterology, Mean age, Original Articles, Surgical procedures, medicine.disease, Surgery, 03 medical and health sciences, Re bleeding, 0302 clinical medicine, Oncology, Anticoagulant therapy, 030220 oncology & carcinogenesis, Cohort, medicine, 030211 gastroenterology & hepatology, Drug intoxication, business
Abstract

The aim of this study was to determine the mortality and re-bleeding rates, and the risk factors involved, in a cohort of patients with previous diverticular bleeding (DB).In 2007, data on 2462 patients with lower gastrointestinal (GI) bleeding were collected prospectively at several French hospitals. We studied the follow-up of patients with DB retrospectively. The following data were collected: age, mortality rates and re-bleeding rates, drug intake, surgery and comorbidities.Data on 365 patients, including 181 women (mean age 83.6 ± 9.8 years) were available. The median follow-up time was 3.9 years (IQR 25-75: 1.7-5.4). Of these, 148 patients died (40.5%). Among the 70 patients (19.2%) who had at least one re-bleeding episode, nine died and three underwent surgical procedures. Anticoagulation and antiplatelet therapy was discontinued in 70 cases (19.2%). The independent risk factors contributing to mortality were age 80 years (HR = 3.18 (2.1-4.9);In this cohort, the rates of mortality and DB re-bleeding after a median follow-up time of 3.9 years were 19.2% and 40.5%, respectively. The majority of the deaths recorded were not due to re-bleeding.

Published
2017

17. 444P PRODIGE 25 (FFCD 11-01)-FOLFA: A randomized phase II trial evaluating aflibercept associated with LV5FU2 regimen as first-line treatment of non-resectable metastatic colorectal cancers

Author

F. Khemissa Akouz, Joëlle Egreteau, K. Le Malicot, Vincent Bourgeois, Nicolas Barriere, M. Baconnier, Jean-Louis Legoux, David Malka, Thomas Aparicio, V. Lorgis, Veronique Guerin-Meyer, David Tougeron, Valérie Boige, V. Lebrun-Ly, Roger Faroux, and Côme Lepage

Subjects
First line treatment, Oncology, medicine.medical_specialty, Regimen, business.industry, Internal medicine, medicine, Hematology, business, Aflibercept, medicine.drug
Published
2020

18. Erratum to ‘Erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial’ [European Journal of Cancer, Volume 124 (January 2020) Pages 91-101]

Author

Fabienne Portales, Olivier Bouché, Roger Faroux, Jérôme Cros, Jean-Philippe Metges, Pascal Hammel, Christine Rebischung, David Tougeron, Christelle De La Fouchardiere, Laurent Mineur, Adam Hamm, Thierry André, Richard Kay, Jean-Baptiste Bachet, Rosine Guimbaud, Christophe Tournigand, Anu Gupta, Iman El Hariry, Thierry Lecomte, Farid El Hajbi, and Christophe Louvet

Subjects
Oncology, Cancer Research, Chemotherapy, medicine.medical_specialty, Asparaginase, Second line treatment, business.industry, medicine.medical_treatment, Cancer, medicine.disease, PHASE IIB TRIAL, chemistry.chemical_compound, Text mining, chemistry, Internal medicine, Pancreatic cancer, Medicine, Open label, business
Published
2020

19. Gemcitabine and Oxaliplatin Chemotherapy or Surveillance in Resected Biliary Tract Cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): A Randomized Phase III Study

Author

Jean-Paul Joly, Eric Assenat, Veronique Guerin-Meyer, Aurélie Bertaut, Jean-Louis Jouve, Jérôme Watelet, Christelle De La Fouchardiere, Catherine Lombard-Bohas, Trevor Stanbury, Karim Boudjema, Eveline Boucher, Laetitia Fartoux, Jean-Marc Phelip, Pascal Hammel, Jean-François Seitz, Karine Bouhier-Leporrier, Jean-Emmanuel Kurtz, M. Benabdelghani, Isabelle Baumgaertner, David Malka, David Tougeron, Roger Faroux, Julien Edeline, Christophe Louvet, Centre Eugène Marquis (CRLCC), Centre Paul Strauss, CRLCC Paul Strauss, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, CHU Pontchaillou [Rennes], Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Strasbourg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Léon Bérard [Lyon], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Mutualiste de Montsouris (IMM), Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Service de gastroentérologie [CHU Saint-Etienne], and Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Time Factors, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, MESH: Antineoplastic Combinated Chemotherapy Protocol / therapeutic uses, Biliary Tract Neoplasms / drug therapy, Biliary Tract Neoplasms / surgery, Deoxycytidine / analogs & derivatives, Oxaliplatin / administration & dosage, Watchful waiting, Deoxycytidine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Progression-free survival, Watchful Waiting, Aged, Aged, 80 and over, Chemotherapy, Biliary tract cancer, business.industry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Middle Aged, Gemcitabine, Progression-Free Survival, 3. Good health, Oxaliplatin, Clinical trial, Biliary Tract Surgical Procedures, Biliary Tract Neoplasms, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Quality of Life, 030211 gastroenterology & hepatology, Female, France, business, Adjuvant, medicine.drug
Abstract

PURPOSE No standard adjuvant treatment currently is recommended in localized biliary tract cancer (BTC) after surgical resection. We aimed to assess whether gemcitabine and oxaliplatin chemotherapy (GEMOX) would increase relapse-free survival (RFS) while maintaining health-related quality of life (HRQOL) in patients who undergo resection. PATIENTS AND METHODS We performed a multicenter, open-label, randomized phase III trial in 33 centers. Patients were randomly assigned (1:1) within 3 months after R0 or R1 resection of a localized BTC to receive either GEMOX (gemcitabine 1,000 mg/m2 on day 1 and oxaliplatin 85 mg/m2 infused on day 2 of a 2-week cycle) for 12 cycles (experimental arm A) or surveillance (standard arm B). Primary end points were RFS and HRQOL. RESULTS Between July 2009 and February 2014, 196 patients were included. Baseline characteristics were balanced between the two arms. After a median follow-up of 46.5 months (95% CI, 42.6 to 49.3 months), 126 RFS events and 82 deaths were recorded. There was no significant difference in RFS between the two arms (median, 30.4 months in arm A v 18.5 months in arm B; hazard ratio [HR], 0.88; 95% CI, 0.62 to 1.25; P = .48). There was no difference in time to definitive deterioration of global HRQOL (median, 31.8 months in arm A v 32.1 months in arm B; HR, 1.28; 95% CI, 0.73 to 2.26; log-rank P = .39). Overall survival was not different (median, 75.8 months in arm A v 50.8 months in arm B; HR, 1.08; 95% CI, 0.70 to 1.66; log-rank P = .74). Maximal adverse events were grade 3 in 62% (arm A) versus 18% (arm B) and grade 4 in 11% versus 3% ( P < .001). CONCLUSION There was no benefit of adjuvant GEMOX in resected BTC despite adequate tolerance and delivery of the regimen.

Published
2019

20. EGFR Expression Is Unreliable to Decide for Cetuximab Treatment in Patients with Metastatic Colorectal Cancer: Results from 'ERBITUX-OUEST'

Author

Corinne Alleaume, F. Grude, Arnaud Uguen, Nacr Eddine Achour, Daniel Ten Martin, Gilles Lemasson, A. Volant, Joseph Politis, Olivier Capitain, Claire Stampfli, Laurent Miglianico, Jérome Chettrit, Jean-François Ramée, Philippe Deguiral, Véronique Verriele, Claire Magois, Norbert Padilla, Annie Wdowik, Sophie Michalak, Murielle Broyer-Petit, Erick Gamelin, Pierre-Luc Etienne, Pierre Marie Girardot, Jean-Philippe Metges, Jean-Jacques Auger, Christian Laboisse, Roger Faroux, Serge Eloit, V. Klein, Fanny Marhuenda, A. Gourlaouen, Marie-Aude Coulon, Delphine Deniel Lagadec, Isabelle Cumin, Louis-Rémi De Ybarlucea, Christian Riche, Bruno Turlin, Olivier Dupuis, Alain Bargain, Eric Lavoine, Ludovic Rosenfeld, Alain Penchet, Jean-Luc Raoul, Jean-Yves Douillard, Viorel Vasiliu, Nathalie Heresbach, Yann Touchefeu, Karine Bideau, and Frédéric Staroz

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, biology, Cetuximab, business.industry, Colorectal cancer, medicine.disease, digestive system diseases, Egfr expression, Oxaliplatin, Irinotecan, 03 medical and health sciences, Regimen, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, biology.protein, Immunohistochemistry, Epidermal growth factor receptor, business, medicine.drug
Abstract

Purpose: Although controversial, assessment of epidermal growth factor receptor (EGFR) expression is required for the approved indications of Cetuximab in metastatic colorectal cancer (mCRC). With the objective of improving patient selection, “ERBITUX-OUEST” study aimed at analyzing EGFR status in a large cohort of mCRC patients who received cetuximab without preliminary EGFR screening, and assessing the correlation between EGFR status and response to treatment retrospectively. Patients and methods: 332 patients treated with Irinotecan Cetuximab based regimen after progression on irinotecan or oxaliplatin therapy were included. EGFR status was assessed using three available immunohistochemistry (IHC) tests and in situ hybridization in case of negativity. Clinical outcomes of EGFR-positive and EGFR-non-detected (or considered as negative with at least one test) patients were compared. Results: Of the 332 samples centrally screened, 194 were classified as full-positive (i.e., EGFR-positive for all three tests), 86 as full-negative, and 52 as discordant. One third of the 131 negative samples with FDA approved test should be reclassified as positive with at least one of the two others tests. Regarding results from FDA approved test only, neither objective response rate (ORR), progression-free survival (PFS) nor overall survival (OS) differed significantly between EGFR-negative and EGFR-positive patients (P = 0.788, 0.326 and 0.888, respectively). Similarly, comparison of full-negative to other groups did not show any significant difference in terms of ORR (P = 0.507), PFS (P = 0.222) or OS (P = 0.686). Conclusion: These data strongly argue against mCRC patients selection for Cetuximab treatment based on EGFR expression as measured by currently available IHC technics.

Published
2016

21. Corrigendum to ‘Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study’

Author

C. Louvet, Christophe Borg, Jaafar Bennouna, Laurent Mineur, F. Marliot, Pierre Laurent-Puig, Franck Pages, J-F. Emile, Alex Duval, Amos Kirilovsky, Julie Henriques, Roger Faroux, Magali Svrcek, Jérôme Galon, Dewi Vernerey, R. Ben Jannet, Aurelie Catteau, Fabienne Hermitte, Julien Taieb, Jérôme Desramé, and Thierry André

Subjects
Oncology, medicine.medical_specialty, business.industry, MEDLINE, Hematology, Predictive value, Oxaliplatin, Stage III Colon Cancer, Internal medicine, medicine, business, Cohort study, medicine.drug
Published
2020

22. 443P First-line chemotherapy with raltitrexed in metastatic colorectal cancer: An AGEO multicentre study

Author

L-J. Palmieri, C. Coutzac, Julien Taieb, Christophe Locher, Olivier Dubreuil, A. Perret, Anthony Turpin, Pascal Artru, A. Pellat, Roger Faroux, Vincent Hautefeuille, Edouard Auclin, Debora Basile, E. Hafliger, Claire Gallois, M. Dior, and Violaine Randrian

Subjects
Oncology, medicine.medical_specialty, business.industry, Colorectal cancer, Internal medicine, Medicine, Hematology, First line chemotherapy, business, medicine.disease, Raltitrexed, medicine.drug
Published
2020

23. 398O Effect of 5 years of imaging and CEA follow-up to detect recurrence of colorectal cancer (CRC) - PRODIGE 13 a FFCD phase III trial

Author

M. Baconnier, Astrid Lièvre, I. Boillot-Benedetto, Sylvain Manfredi, Emilie Barbier, Philippe Deguiral, Eric Terrebonne, L. Cany, M. Benabdelghani, C. Lepage, Denis Pezet, J. Ain, Antoine Adenis, Roger Faroux, O. Bouche, P. Prost, J.-C. Duchmann, Gilles Breysacher, J.M. Phelip, and A. Pelaquier

Subjects
Oncology, medicine.medical_specialty, Colorectal cancer, business.industry, Internal medicine, medicine, Hematology, medicine.disease, business
Published
2020

24. Comparison of 4 Screening Methods for Detecting Fluoropyrimidine Toxicity Risk: Identification of the Most Effective, Cost-Efficient Method to Save Lives

Author

Tamara Matysiak Budnik, Jean-Philippe Metges, Hélène Senellart, Olivier Capitain, Roger Faroux, Marc Ferec, Mario Campone, Jonathan Dauve, Nadege Blouin, Valérie Rossi, Valérie Seegers, and Claire Stampfli

Subjects
Oncology, medicine.medical_specialty, Health, Toxicology and Mutagenesis, DPD deficiency, fluoropyrimidines, Toxicology, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Screening method, medicine, Dihydropyrimidine dehydrogenase, Chemical Health and Safety, Cost efficiency, business.industry, screening, lcsh:RM1-950, Public Health, Environmental and Occupational Health, Risk identification, toxicity, risk assessment, lcsh:Therapeutics. Pharmacology, comparison, 030220 oncology & carcinogenesis, Toxicity, Original Article, Risk of death, Risk assessment, business
Abstract

Background: Fluoropyrimidines (FPs) carry around 20% risk of G3-5 toxicity and 0.2-1% risk of death, due to dihydropyrimidine dehydrogenase (DPD) deficiency. Several screening approaches exist for predicting toxicity, however there is ongoing debate over which method is best. This study compares 4 screening approaches. Method: 472 patients treated for colorectal, head-and-neck, breast, or pancreatic cancers, who had not been tested pre-treatment for FP toxicity risk, were screened using: DPYD genotyping (G); phenotyping via plasma Uracil (U); phenotyping via plasma-dihydrouracil/uracil ratio (UH2/U); and a Multi-Parametric Method (MPM) using genotype, phenotype, and epigenetic data. Performance was compared, particularly the inability to detect at-risk patients (false negatives). Results: False negative rates for detecting G5 toxicity risk were 51.2%, 19.5%, 9.8% and 2.4%, for G, U, UH2/U and MPM, respectively. False negative rates for detecting G4-5 toxicity risk were 59.8%, 36.1%, 21.3% and 4.7%, respectively. MPM demonstrated significantly (p < 0.001) better prediction performance. Conclusion: MPM is the most effective method for limiting G4-5 toxicity. Its systematic implementation is cost-effective and significantly improves the risk-benefit ratio of FP-treatment. The use of MPM, rather than G or U testing, would avoid nearly 8,000 FP-related deaths per year globally (500 in France), and spare hundreds of thousands from G4 toxicity.

Published
2020

25. Skeletal muscle loss under chemotherapy and its association with survival and systemic treatment toxicity in metastatic colorectal cancer: An AGEO prospective multicenter study

Author

Claire Gallois, Astrid Lièvre, Pascal Artru, Lysiane Marthey, Maximilien Barret, Simon Pernot, Julien Taieb, Camille Bourillon, Thierry Lecomte, Christophe Locher, Edouard Auclin, and Roger Faroux

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, business.industry, Colorectal cancer, medicine.medical_treatment, Skeletal muscle, medicine.disease, medicine.anatomical_structure, Multicenter study, Internal medicine, Toxicity, medicine, business
Abstract

4025 Background: We showed in a previous work that “Patient Generated-Subjective Global Assessment” (PG-SGA) was independently associated with survival and treatment toxicities in non-pretreated metastatic colorectal cancer (mCRC) patients. We have evaluated here if muscle mass in these patients can provide useful additional information for clinical practice. The objective of the present work was to evaluate the association between baseline sarcopenia, and the variation of the Skeletal Muscle Index (SMI) under treatment with survival and chemotherapy-related toxicities in our population of non-pretreated mCRC patients. Methods: This prospective multicenter observational study enrolled non-pretreated mCRC patients. Measurement of SMI was performed on routine CT scan at day 0 (D0) and day 60 (D60). PG-SGA score and other nutritional factors were collected at D0. Progression-free survival (PFS) and overall survival (OS) were calculated from treatment start. Treatment related toxicities were registered according to the NCI CTCAE v4.0. Results: 149 patients were included in eight French centers from 7/2013 to 11/2016. Sarcopenia at baseline was not significantly associated with survival outcomes or chemotherapy-related toxicities. The best cut-point value of SMI variation (between D0 and D60) for OS prediction obtained with a log-rank maximisation method was -14%. The decrease in SMI > 14%, with a median follow-up of 23 months, was significantly associated with shorter PFS (6 vs 9 mo; HR 1.8, 95%CI 1.1-3.1, p = 0.02) and OS (8.5 vs 26 mo; HR 2.4, 95%CI 1.3-4.4, p = 0.004), independently of hypoalbuminemia and malnutrition defined by PG-SGA, in multivariate analysis. 40% of patients with a SMI decrease > 14%, and 22% of patients with a SMI increase or stable or decrease < 14% developed grade ≥ 2 clinical toxicities (OR 3.0, 95%CI 1.2-7.7, p = 0.02), but the difference was not statistically significant in multivariate analysis (OR 2.3. 95%CI 0.8-6.7, p = 0.1). Conclusions: To our knowledge, this study is the first study assessing the association of skeletal muscle loss with survival and treatment toxicities in patients with mCRC prospectively. In our population of non pre-treated mCRC patients, baseline sarcopenia was not associated with poor survival outcomes, but the decrease in SMI > 14% during the first two months of treatment was significantly associated with decreased PFS and OS, independently of other prognostic and nutritional factors.

Published
2020

26. Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with mFOLFOX6 (three versus six months) in the prospective IDEA France cohort study (PRODIGE-GERCOR)

Author

Laurent Mineur, Thierry André, Pierre Laurent-Puig, Magali Svrcek, Jérôme Galon, Julien Taieb, Jean-François Emile, Jaafar Bennouna, Roger Faroux, Dewi Vernerey, Rim Ben Jannet, Alex Duval, Fabienne Hermitte, Jérôme Desramé, Florence Marliot, Franck Pagès, Aurelie Catteau, Julie Henriques, Christophe Louvet, and Christophe Borg

Subjects
Oncology, Cancer Research, medicine.medical_specialty, business.industry, Predictive value, Stage III Colon Cancer, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Medicine, business, 030215 immunology, Cohort study
Abstract

10 Background: In stage III colon cancer patients treated with CAPOX, 3 months of therapy was as effective as 6 months. It was not the case for those receiving mFOLFOX6. We assessed the prognostic and predictive value of the Immunoscore (IS) in the mFOLFOX6 subgroup (90% of patients enrolled) of the IDEA France cohort study. Methods: 1200 patients randomly assigned to 3 months (n = 593) or 6 months (n = 607) of mFOLFOX6, with available tumor sample, were included. Densities of CD3+ and cytotoxic CD8+ T-cells in the tumor and invasive margin were determined by immunohistochemistry, quantified by digital pathology, and converted to IS using the pre-defined cut-off. The IS performance to predict disease-free survival (DFS) was assessed in each arm and adjusted in multivariate Cox models. Results: In a two-category IS analysis, Low and (Int+High) IS were observed in 423 (43.5%) and 550 (56.5%) patients, respectively. Low IS identified patients with higher-risk of relapse or death (HR = 1.60; 95% CI 1.27-2.01, P < 0.0001). The 3-year DFS was 66.34% (95% CI 61.54-70.69) and 77.66% (95% CI 73.86-80.97) for Low and (Int+High) IS, respectively. In multivariate analysis, IS remained independently associated with DFS (P = 0.0007) when combined with T/N stage. A statistically significant interaction was observed for the IS predictive value for treatment duration (3 vs 6 months) in term of DFS in the whole population (P = 0.0566) and TN subgroups (Low-risk T1-3, N1 vs High-risk T4 and/or N2; P = 0.0015). The 3-year DFS of patients with (Int+High) IS in the 3-month arm was 71.5% (95% CI 65.7-76.6) versus 83.8% (95% CI, 78.8-87.8) in the 6-month arm (HR = 0.528; 95% CI 0.372-0.750; log-rank P = 0.0004); the benefit retained in low-risk and high-risk patients (all P≤0.010). 6-month mFOLFOX6 showed no significant benefit for patients with Low IS (HR = 0.836, log-rank P = 0.269). Conclusions: The IS prognostic value in patients treated with mFOLFOX6 was confirmed. Its predictive value for benefit of longer duration treatment, despite a strong statistical signal, needs to be confirmed in an external validation cohort. Clinical trial information: NCT03422601.

Published
2020

27. Pravastatin combination with sorafenib does not improve survival in advanced hepatocellular carcinoma

Author

Jean-Pierre Bronowicki, Jean-Louis Legoux, Thierry Lecomte, Jean-François Seitz, Olivier Bouché, Sylvain Manfredi, Prodige Investigators, Emilie Barbier, Jean-Marc Phelip, Eric Nguyen Khac, Ghassan Riachi, Isabelle Ollivier-Hourmand, Jacques Denis, Jean-Louis Jouve, Julien Vergniol, Anne-Laure Villing, Maryline Debette-Gratien, Jean-François Ramée, Roger Faroux, and Faiza Khemissa Akouz

Subjects
0301 basic medicine, Oncology, Sorafenib, Adult, Diarrhea, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Antineoplastic Agents, Kaplan-Meier Estimate, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, neoplasms, Aged, Pravastatin, Aged, 80 and over, Univariate analysis, Hepatology, Performance status, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Prognosis, digestive system diseases, Progression-Free Survival, Clinical trial, 030104 developmental biology, Hepatocellular carcinoma, Quality of Life, 030211 gastroenterology & hepatology, Female, business, Liver cancer, medicine.drug, Follow-Up Studies
Abstract

Background & Aims Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC). Combining sorafenib with another treatment, to improve overall survival (OS) within an acceptable safety profile, might be the next step forward in the management of patients with advanced HCC. We aimed to assess whether a combination of sorafenib and a statin improved survival in patients with HCC. Methods The objective of the PRODIGE-11 trial was to compare the respective clinical outcomes of the sorafenib-pravastatin combination (arm A) versus sorafenib alone (arm B) in patients with advanced HCC. Child-Pugh A patients with advanced HCC who were naive to systemic treatment (n = 323) were randomly assigned to sorafenib-pravastatin combination (n = 162) or sorafenib alone (n = 161). The primary endpoint was OS; secondary endpoints were progression-free survival, time to tumor progression, time to treatment failure, safety, and quality of life. Results After randomization, 312 patients received at least 1 dose of study treatment. After a median follow-up of 35 months, 269 patients died (arm A: 135; arm B: 134) with no difference in median OS between treatments arms (10.7 months vs. 10.5 months; hazard ratio = 1.00; p = 0.975); no difference was observed in secondary survival endpoints either. In the univariate analysis, the significant prognostic factors for OS were CLIP score, performance status, and quality of life scores. The multivariate analysis showed that the only prognostic factor for OS was the CLIP score. The main toxicity was diarrhea (which was severe in 11% of patients in arm A, and 8.9% in arm B), while severe nausea-vomiting was rare, and no toxicity-related deaths were reported. Conclusion Adding pravastatin to sorafenib did not improve survival in patients with advanced HCC. Lay summary Sorafenib has proven efficacy for the treatment of patients with advanced hepatocellular carcinoma. However, overall survival remains poor in these patients, so we were interested to see if the addition of a statin, pravastatin, improved outcomes in patients with advanced HCC. This randomized-controlled trial demonstrated that the sorafenib-pravastatin combination did not improve overall survival in this study population compared to sorafenib alone. Clinical trial number: NCT01075555.

Published
2018

28. Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials

Author

Mireille Mousseau, Eric Francois, A. Fatisse, A. Bedjaoui, Abakar Mahamat, C. Lombard-Bohas, J. Ezenfis, Marc Porneuf, F. Subtil, M. Tissot, Emilie Maillard, M. Fayolle, J.F. Dor, A. Votte, P. Chiappa, P. Prost, Denis Cléau, P. Bergerault, J.C. Souquet, K. Beerblock, P. Chatrenet, J.M. Sabate, M. Carreiro, S. Beorchia, Vincent Hautefeuille, Jessika Moreau, N. Delas, C. Vilain, Christian Borel, Franck Audemar, M. Duluc, Touraj Mansourbakht, Bernard Denis, Gael Deplanque, Jean-Marc Phelip, C. Brezault, Anne Thirot-Bidault, L. Gasnault, Jean-Louis Jouve, Y. Rinaldi, B. Leduc, Y. Courouble, A. Alessio, Matthieu Schnee, P. Cassan, Antoine Adenis, Jocelyne Provencal, A. Botton, Laurent Cany, Françoise Desseigne, Marie-Christine Kaminsky, Mohamed Ramdani, B. Lafforgue, L. Rob, J.C. Barbare, S. Jacquot, A. Zaanan, J.-Y. Douillard, C. Cornila, B. Rhein, Benjamin Linot, Z. Ladhib, D. Zylberait, Cedric Lecaille, N. Hess-Laurens, H. Brixi-Benmansour, C. Rebischung, C. Giraud, L. Stefani, D. Pillon, J.P. Lafargue, J. Forestier, P. Laplaige, C. Paoletti, S. Lavau Denes, Etienne Suc, A. Patenotte, E. Echinard, François-Xavier Caroli-Bosc, D. Goldfain, V. Quentin, Hervé Perrier, J.D. Grangé, A. Marre, M. Baconnier, Bruno Coudert, Thomas Walter, R. Benoit, A. Blanchi, A.C. Dupont-Gossart, Emilie Barbier, X. Coulaud, D. Besson, Isabelle Trouilloud, D. Sevin-Robiche, M Giovannini, O. Boulat, C. Lobry, H. Castanie, Y. Molin, Thomas Aparicio, Valérie Boige, P. Lehair, J.P. Robin, J.P. Latrive, J. Goineau, Clément Belletier, G. Medinger, C. Lepere, Philippe Rougier, N. Bouaria, E. Carola, V. Derias, Bernard Paillot, Yves Becouarn, F. Kikolski, Martin Combe, Julie Vincent, C. Briac-Levaché, C. Becht, François Ghiringhelli, J. Charneau, Dany Gargot, Julien Vergniol, Denis Péré-Vergé, P. Pienkowski, Patrick Texereau, I. Baumgaertner, J.P. Ramain, Pierre-Luc Etienne, P. Claudé, Jean Francois Paitel, J.P. Plachot, M.-C. Clavero-Fabri, P. Geoffroy, A. Cadier-Lagnes, Y. Le Bricquir, S. Fratte, O. Favre, Aimery de Gramont, J. Butel, David Tougeron, B. Winkfield, E. Janssen, J. Meunier, Julien Volet, N. Gérardin, D. Soubrane, Vincent Bourgeois, Xavier Adhoute, Y.H. Lam, P.A. Haineaux, A. Rotenberg, J-B. Bachet, C. Berger, F. Almaric, J. Tuaillon, G. Gatineau-Saillant, F. Zerouala-Boussaha, E. Cuillerier, R. Lamy, D. Luet, D. Baudet-Klepping, E.A. Pariente, M. Gignoux, J. Martin, M. Blasquez, Romain Coriat, C. Bineau, J. Boutin, A. Aouakli, F. Dewaele, A.M. Queuniet, V. Sebbagh, P. Couzigou, N. Barrière, Faiza Khemissa, P. Follana, Laurence Chone, F. Petit-Laurent, N. Abdelli, Olivier Capitain, D. Bechade, Corinne Sarda, J.P. Herr, P. Pouderoux, Julien Taieb, M. Pauwels, E. Zrihen, L. Wander, Gael Goujon, G. Boilleau-Jolimoy, Anne Thirot Bidault, B. Landi, V. Jestin Le Tallec, Jaafar Bennouna, O. Berthelet, M. Glikmanas, H. Salloum, Côme Lepage, Thierry Lecomte, P. Amoyal, C. Platini, Veronique Guerin-Meyer, B. Garcia, Laetitia Dahan, Pascal Burtin, J. Villand, S. Nguyen, A. Roussel, F. Di Fiore, S. Oddou-Lagraniere, J.P. Aucouturier, Veronique Lorgis, Gerard Cavaglione, J.P. Lagasse, Dominique Auby, Pierre Michel, F. Bonnetain, Gilles Breysacher, R. Mackiewicz, Philippe Ruszniewski, T. Morin, J. Thaury, Clara Locher, J.M. Vantelon, S. Nasca, J.P. Barbieux, H. Maechel, Y. Coscas, May Mabro, S. Montembault, P. Novello, M. Charbit, J. Deguiral, A. Gagnaire, D. Festin, A. Gueye, Hélène Senellart, Achim Weber, Nadia Bouarioua, Jérôme Dauba, Michel Ducreux, Jean-Luc Raoul, G. Coulanjon, J.N. Vaillant, S. Chaussade, A. Gilbert, Anne-Laure Villing, Dominique Genet, P. Martin, M. Ben Abdelghani, M.P. Galais, A. Azzedine, A. Lemaire, C. Barberis, C. Buffet, J. Egreteau, G. Roquin, M. Mornet, Isabelle Cumin, M. Pelletier, P. Feydy, J. Lacourt, T. Chatellier, Jean-Louis Legoux, M. Benchalal, I. Graber, S. Nahon, P. Pantioni, A. Hollebecque, M. Zawadi, Pascal Hammel, M. Mignot, Roger Faroux, J. Lafon, Mohamed Gasmi, Jean-Philippe Spano, S. Pesque-Penaud, C. de la Fouchardiere, J. Cretin, Olivier Bouché, D. Smith, E. Norguet-Monnereau, G. Bordes, Sylvain Manfredi, Thévenet P, Herve Lacroix, E. Dorval Danquechin, Eric Terrebonne, Laurent Bedenne, P. Godeau, David Malka, V. Veuillez, Emmanuel Mitry, F. Riot, Sandrine Hiret, François Morvan, M.C. Gouttebel, Jean-François Seitz, Karine Bouhier-Leporrier, N. Stremsdoerfer, P. Souillac, M. Mozer, C. Couffon, F. Husseini, J.M. Cheula, J.-M. Gornet, K. Slimane Fawzi, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Université Paris-Saclay, Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), CHD Vendee (La Roche Sur Yon), Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Privé des Côtes d'Armor (HPCA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut de Cancérologie de la Loire [Saint-Priest en Jarez], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Service d'hépato-gastro-entérologie et oncologie digestive [CHR Orléans], Centre Hospitalier Régional d'Orléans (CHRO), Service De Gastroenterologie, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Hôpital Louis Pasteur [Colmar] (CH Colmar), Département d'hépato-gastro-entérologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut des Maladies de l’Appareil Digestif [CHU Nantes], Service d'oncologie [Institut Hospitalier Franco-Britannique : Levallois-Perret], Institut hospitalier Franco-Britannique [Levallois-Perret], Département d'oncologie médicale (CHU Robert Debré, Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN)

Subjects
Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, Angiogenesis Inhibitors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Overweight, Gastroenterology, Pooled analysis, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Outcome Assessment, Health Care, Individual data, medicine, Overall survival, Humans, Neoplasm Metastasis, Objective response, Aged, 2. Zero hunger, Clinical Trials as Topic, Prognostic factor, business.industry, nutritional and metabolic diseases, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Prognosis, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, Normal weight, 030220 oncology & carcinogenesis, Female, medicine.symptom, Colorectal Neoplasms, business, medicine.drug
Abstract

IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI

Published
2018

29. Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, Phase III Trial

Author

Jaafar Bennouna, Yves Becouarn, C. Lepere, for Prodige investigators, Gercor, Fédération Française de Cancérologie Digestive, Laurent Mineur, Gaël Deplanque, Aimery de Gramont, Louis Marie Dourthe, Ahmed Khalil, Joëlle Egreteau, Marine Hug de Larauze, Unicancer, Jean-Baptiste Bachet, Roger Faroux, Jérôme Desramé, Olivier Dupuis, S. Fratte, Jeremie Bez, Thierry André, Marc Ychou, François Ghiringhelli, Olivier Bouché, May Mabro, Julien Taieb, Dewi Vernerey, Marie Pierre Galais, Christophe Louvet, Jérôme Dauba, Sophie Paget-Bailly, Franck Bonnetain, Benoist Chibaudel, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut Sainte Catherine [Avignon], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Hôpital privé Jean Mermoz, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CH Belfort-Montbéliard, Fédération Francophone de la Cancérologie Digestive, FFCD, Centre Hospitalier Layné, Institut Mutualiste de Montsouris (IMM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Clinique Victor Hugo, Institut Bergonié [Bordeaux], Hôpital Foch [Suresnes], Groupe Hospitalier Bretagne Sud (GHBS), Hôpital universitaire Robert Debré [Reims], Groupe Hospitalier Paris Saint-Joseph, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Clinique Sainte Anne [Strasbourg], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], Institut hospitalier Franco-Britannique [Levallois-Perret], Université Sorbonne Paris Cité (USPC), Université Paris Descartes - Paris 5 (UPD5), CHU Saint-Antoine [APHP], Groupe cooperateur multidisciplinaire en oncologie (GERCOR), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Inserm UMR 1098, Centre René Gauducheau - ICO, institut de Cancerologie de l'Ouest, Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut Bergonié - CRLCC Bordeaux, centre hospitalier Bretagne sud, Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), CHU Pitié-Salpêtrière [APHP], and CHU Tenon [APHP]

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, Capecitabine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Clinical endpoint, medicine, education, education.field_of_study, Chemotherapy, business.industry, medicine.disease, 3. Good health, Oxaliplatin, 030104 developmental biology, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, business, Adjuvant, medicine.drug
Abstract

Purpose Reduction of adjuvant treatment duration may decrease toxicities without loss of efficacy in stage III colon cancer. This could offer clear advantages to patients and health care providers. Methods In International Duration Evaluation of Adjuvant Chemotherapy (IDEA) France, as part of the IDEA international collaboration, patient with colon cancer patients were randomly assigned to 3 and 6 months of modified FOLFOX6 (mFOLFOX6: infusional fluorouracil, leucovorin, and oxaliplatin) or capecitabine plus oxaliplatin (CAPOX) by physician choice. The primary end point was disease-free survival (DFS), and analyses were descriptive. Results A total of 2,010 eligible patients received either 3 or 6 months of chemotherapy (modified intention-to-treat population); 2,000 (99%) had stage III colon cancer (N1: 75%, N2: 25%); 1,809 (90%) received mFOLFOX6, and 201 (10%) received CAPOX. The median age was 64 years, and the median follow-up time was 4.3 years. Overall, 94% (3 months) and 78% (6 months) of patients completed treatment (fluoropyrimidines ± oxaliplatin). Maximal grade 2 and 3 neuropathy rates were 28% and 8% in the 3-month arm and 41% and 25% in the 6-month arm ( P < .001). Final rates of residual neuropathy greater than grade 1 were 3% in the 3-month arm and 7% in the 6-month arm ( P < .001). There were 578 DFS events: 314 and 264 in the 3- and 6-month arms, respectively. The 3-year DFS rates were 72% and 76% in the 3- and 6-month arms, respectively (hazard ratio [HR], 1.24; 95% CI, 1.05 to 1.46; P = .0112). In the 3 and 6-month arms, respectively, for patients who received mFOLFOX6, the 3-year DFS rates were 72% and 76% (HR, 1.27; 95% CI, 1.07 to 1.51); for the T4 and/or N2 population, they were 58% and 66% (HR, 1.44; 95% CI, 1.14 to 1.82); and for the T1-3N1 population, they were 81% and 83% (HR, 1.15; 95% CI, 0.89 to 1.49). Conclusion IDEA France, in which 90% of patients received mFOLFOX6, shows superiority of 6 months of adjuvant chemotherapy compared with 3 months, especially in the T4 and/or N2 subgroups. These results should be considered alongside the international IDEA collaboration data.

Published
2018

30. Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9)

Author

Stephane Jacquot, Karine Le Malicot, Christian Borel, Julien Taieb, Valérie Boige, Thomas Aparicio, Jean-Marc Phelip, Dominique Genet, Jaafar Bennouna, Laetitia Dahan, Roger Faroux, Etienne Suc, Faiza Khemissa, E. Francois, Côme Lepage, Prodige Investigators, François Ghiringhelli, Patrick Texereau, Françoise Desseigne, Olivier Bouché, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] (CGFL), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut Gustave Roussy (IGR), Fédération Francophone de la Cancérologie Digestive, FFCD, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, CRLCC Paul Strauss, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Polyclinique de Limoges - Site Émailleurs-Colombier [Limoges], Centre Hospitalier Saint Jean de Perpignan, Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Centre Léon Bérard [Lyon], CHU Mont de Marsan, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, université de Bourgogne, LNC, UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), CHU Saint Louis [APHP], Université Sorbonne Paris Cité ( USPC ), Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] ( CGFL ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institut Gustave Roussy ( IGR ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), CRLCC Antoine Lacassagne, Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Clinique Saint Jean Languedoc, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Institut de Cancérologie de l'Ouest

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, Time Factors, Bevacizumab, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, law.invention, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, [SDV.CAN] Life Sciences [q-bio]/Cancer, Randomized controlled trial, law, Internal medicine, medicine, Humans, Neoplasm Metastasis, Aged, Chemotherapy, business.industry, Induction chemotherapy, Induction Chemotherapy, Middle Aged, medicine.disease, 3. Good health, Irinotecan, Regimen, 030104 developmental biology, Fluorouracil, 030220 oncology & carcinogenesis, Female, business, Colorectal Neoplasms, Metastatic Colorectal Cancer, medicine.drug
Abstract

Purpose Conflicting results are reported for maintenance treatment with bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal cancer after induction chemotherapy. Patients and Methods In this open-label, phase III, randomized controlled trial, we compared the tumor control duration (TCD) observed with bevacizumab maintenance and with no treatment (observation) during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil, leucovorin, and irinotecan plus bevacizumab. After disease progression, the induction regimen was repeated for eight cycles, followed by a new CFI. Results From March 2010 to July 2013, 491 patients were randomly assigned. Disease progression or death occurred during induction chemotherapy in 85 patients (17%); 261 patients (53%) had at least one reinduction, 107 (22%) had two reinductions, and 56 (11%) had three or more reinductions. The median TCD was 15 months in both groups; the median progression-free survival (PFS) from randomization was 9.2 and 8.9 months in the maintenance group and observation groups, respectively. The TCD observed in both groups was higher compared with the TCD hypotheses of the trial. The median overall survival (OS) was 21.7 and 22.0 months in the maintenance and observation groups, respectively. In the per-protocol population, defined as patients with at least one reinduction after the first progression, the median duration of the first CFI was 4.3 months in both arms; the median TCD was 17.8 and 23.3 months ( P = .339), the median PFS was 9.9 and 9.5 months, and the median OS was 27.6 and 28.5 months in the maintenance and observation groups, respectively. Multivariable analysis revealed that female gender, WHO performance status ≥ 2, and unresected primary tumors were associated with a shorter TCD. Conclusion Bevacizumab maintenance monotherapy did not improve TCD, CFI duration, PFS, or OS.

Published
2018

31. Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20 study results

Author

Julien Taieb, Roger Faroux, M. Baconnier, Laurent Bedenne, Alice Oden-Gangloff, Elena Paillaud, F. Khemissa Akouz, F. Retornaz, Sandrine Lavau-Denes, F. El Hajbi, P.L. Etienne, Christophe Locher, O. Bouche, S. Kirscher, E. Maillard, Yves Rinaldi, Thomas Aparicio, Dominique Genet, E. Francois, Thierry Lecomte, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Sorbonne Paris Cité ( USPC ), Service d'hépato-gastro-entérologie et cancérologie digestive [CHU de Reims], Centre Hospitalier Universitaire de Reims ( CHU de Reims ), Service de chirurgie digestive, générale et cancérologique [Hôpital européen Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Fédération Francophone de la Cancérologie Digestive, FFCD, Institut Sainte Catherine [Avignon], Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, CRLCC Oscar Lambret, Service des maladies de l'appareil digestif (CH Meaux), CH Meaux, Service de gastro-entérologie (Hôpital Européen de Marseille), Hôpital Européen [Fondation Ambroise Paré - Marseille], Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), CHU Dupuytren, Service d'hépato-gastro-entérologie et endoscopies (CH Annecy), CH Annecy Genevois, CHU Rouen, Polyclinique de Limoges - site François Chénieux [Limoges], Unité de médecine gériatrique ( Gériatrie - Henri Mondor ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Laboratoire de Physique Atmosphérique et Planétaire ( LPAP ), Université de Liège, CRLCC Antoine Lacassagne, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de chirurgie digestive, générale et cancérologique [CHU HEGP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Normandie Université (NU), Unité de médecine gériatrique (Gériatrie - Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Laboratoire de Physique Atmosphérique et Planétaire (LPAP), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Université de Lille-UNICANCER, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)

Subjects
Male, Organoplatinum Compounds, Colorectal cancer, Leucovorin, law.invention, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Randomized controlled trial, FOLFOX, law, Antineoplastic Combined Chemotherapy Protocols, randomized trial, Neoplasm Metastasis, Aged, 80 and over, education.field_of_study, Standard treatment, Age Factors, Hematology, Corrigenda, 3. Good health, Bevacizumab, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Fluorouracil, Colorectal Neoplasms, medicine.drug, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, colorectal cancer, elderly, 03 medical and health sciences, Internal medicine, Gastrointestinal Tumors, medicine, FOLFIRI Regimen, Humans, education, Survival rate, Aged, business.industry, antiangiogenic, Original Articles, medicine.disease, composite criteria, Camptothecin, business
Abstract

IF 11.855; International audience; Background :Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population.Patients and methods :Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator’s choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria.Results :About 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75–91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT).Conclusion :Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.

Published
2018

32. Risk factors for hepatocellular carcinoma in Caucasian patients with non-viral cirrhosis: the importance of prior obesity

Author

Sébastien Küry, Isabelle Archambeaud, Didier Samuel, Hélène Aublé, Cyrille Feray, Jérôme Gournay, Guillaume Fallot, Lucie Planche, Roger Faroux, and Pierre Nahon

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cirrhosis, Alcohol Drinking, Population, Gastroenterology, White People, Body Mass Index, Liver disease, Sex Factors, Liver Cirrhosis, Alcoholic, Risk Factors, Internal medicine, Diabetes Mellitus, Odds Ratio, Humans, Medicine, Obesity, Prospective Studies, education, Life Style, Aged, education.field_of_study, Hepatology, business.industry, Liver Neoplasms, Smoking, Age Factors, Middle Aged, Hepatitis B, medicine.disease, digestive system diseases, Cross-Sectional Studies, Logistic Models, Case-Control Studies, Hepatocellular carcinoma, Elevated transaminases, Female, France, business, Viral hepatitis, Body mass index
Abstract

Background & Aims In patients with cirrhosis, the risk of hepatocellular carcinoma (HCC) depends upon age, gender and the etiology of liver disease. Few studies are available in Caucasian patients with alcoholic or metabolic cirrhosis without viral hepatitis. Methods Cross-sectional clinical data from 905 HCV- and HBV-negative Caucasian patients with alcoholic or metabolic cirrhosis were prospectively collected in four French centres. The risk factors for HCC were identified by logistic regression analysis in the whole population and in a nested case–control study. Results The etiology of cirrhosis was alcoholic (48%), metabolic (7%) or mixed (45%). Patients were predominantly male (80%), mean age 62 years old and 31% had HCC. Mean body mass index (BMI) was 27 ± 5 and 30% were obese at inclusion. The maximum BMI reached throughout life was 31 ± 6 and 63% had been obese. Ninety percent of the population had daily alcohol consumption, 73% were smokers. Hepatocellular carcinoma was independently related to male gender (P

Published
2015

33. Predictive factors for early progression during induction chemotherapy (IC) and chemotherapy-free interval (CFI): Analysis from PRODIGE 9 trial

Author

E. Francois, Oana Cojocarasu, Joëlle Egreteau, Côme Lepage, Julien Taieb, K. Le Malicot, Thomas Aparicio, Veronique Guerin-Meyer, François Ghiringhelli, O. Bouche, Jaafar Bennouna, J-B. Bachet, Laetitia Dahan, M-C. Kaminsky-Forrett, Christian Borel, J.M. Phelip, Roger Faroux, Mohamed Gasmi, J.-M. Gornet, Valérie Boige, Service d'hépato-gastro-entérologie, cancérologie digestive et assistance nutritionnelle [CHU de Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Fédération Francophone de la Cancérologie Digestive, FFCD, Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hépato-Gastro Entérologie et Oncologie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), département d'oncologie médicale (CHU Robert Debré, Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'oncologie médicale (Centre Antoine Lacassagne, Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Paul Strauss de Lutte contre le Cancer (Strasbourg), Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), CHD Vendee (La Roche Sur Yon), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'oncologie medicale (CH Bretagne Sud, Lorient), CH Bretagne Sud, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hémato-oncologie (CH du Mans), Centre Hospitalier du Mans, Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Service d'Oncologie Médicale [Angers], Centre Paul Papin, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service Biostatistiques et Informatique Médicale (CHU de Dijon) ( DIM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Antoine Lacassagne de Nice, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'oncologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Aix Marseille Université ( AMU ) -Hôpital Saint-Joseph [Marseille], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
Oncology, 0303 health sciences, Chemotherapy, medicine.medical_specialty, business.industry, medicine.medical_treatment, Induction chemotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, 3. Good health, Free interval, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Predictor variable, business, 030304 developmental biology
Abstract

IF 11.855; International audience

Published
2017

34. Evaluating lanreotide as maintenance therapy after first-line treatment in patients with non-resectable duodeno-pancreatic neuroendocrine tumours

Author

Marianne Pavel, Denis Smith, M. Ducreux, Astrid Lièvre, Karine Bouhier-Leporrier, Karine Le Malicot, Jean-Louis Legoux, Anja Rinke, Olivia Hentic, Juan W. Valle, Nadia Bouarioua, Christos Toumpanakis, Guillaume Cadiot, David Tougeron, Thomas Walter, Rosine Guimbaud, Laetitia Dahan, Frédéric Di Fiore, Côme Lepage, Ivan Borbath, Roger Faroux, Jean-Yves Scoazec, Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Fédération Francophone de la Cancérologie Digestive, FFCD, Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Hôpital de la Timone [CHU - APHM] (TIMONE), Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital, Regional Hospital of Orleans, Service de Biostatistique, Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Bases moléculaires de la réponse aux xénobiotiques (U775 (IFR95)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France, affiliation inconnue, Service d'Oncologie Médicale, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Hospitalier Départemental Les Oudairies, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'Oncologie Médicale, Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital de la Timone [CHU - APHM] ( TIMONE ), Hôpital Charles Nicolle [Rouen]-CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Bases moléculaires de la réponse aux xénobiotiques ( U775 (IFR95) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Fédération Francophone de Cancérologie Digestive (FFCD), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Oncology, Male, Duodenopancreatic neuroendocrine tumours, medicine.medical_treatment, Lanreotide, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, chemistry.chemical_compound, 0302 clinical medicine, Quality of life, Maintenance therapy, Clinical Protocols, Duodenal Neoplasms, Prospective Studies, Prospective cohort study, Gastroenterology, Middle Aged, 3. Good health, Europe, Clinical trial, Neuroendocrine Tumors, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Somatostatin, Adult, medicine.medical_specialty, Randomization, Adolescent, Maintenance, 030209 endocrinology & metabolism, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, Peptides, Cyclic, Disease-Free Survival, 03 medical and health sciences, Young Adult, Double-Blind Method, Internal medicine, medicine, Humans, Aged, Chemotherapy, Hepatology, business.industry, Surgery, Pancreatic Neoplasms, First line, chemistry, Quality of Life, business
Abstract

Introduction Patients with metastatic or locally advanced, non-resectable, grade 1 or 2 well-differentiated duodeno-pancreatic (WDDP) NETs are treated following European guidelines. Patients (Pts) with aggressive disease, i.e. progressive and/or symptomatic metastases and/or with significant hepatic invasion (>30–50%), and/or bone metastases, anti-tumour therapy should receive systemic combination of chemotherapy once disease control is obtained. Aim(s) The aim is to stop chemotherapy until progression. REMINET is an academic randomized, double-blind, placebo-controlled, phase II/III study designed to evaluate lanreotide (LAN) as maintenance treatment after L1 chemotherapy in G1-G2 WDDP NET. Materials and methods Main eligibility criteria: adults pts with a metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 1 or 2 WDDP NETs and documented control disease after L1 therapy at least 4 weeks prior to randomization. Results 222 patients will be randomly assigned in a 1:1 ratio to receive 120 mg LAN or placebo, every 28 days, until disease progression or unacceptable toxicity. The aim of the phase II part is to demonstrate a 6-months PFS >45% in LAN arm. Secondary endpoints are PFS according to central review, overall survival, safety and quality of life. A bio-bank of frozen blood will be constituted. Conclusion The study is currently open in France, Germany, Belgium, United Kingdom and Ireland. A total of 25 patients are randomized (NCT02288377).

Published
2017

35. A multicenter phase II study of personalized FOLFIRI-cetuximab for safe dose intensification

Author

Michèle Boisdron-Celle, Claude Masliah, Antoine Adenis, Jean Philippe Metges, Olivier Capitain, Virginie Berger, You Heng Lam, Jean-Luc Raoul, Erick Gamelin, Roger Faroux, Anne Lise Poirier, Thierry Lecomte, Alain Morel, Laboratoire d'Oncopharmacologie (Département de Pharmacogénétique), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, CRLCC Centre Paoli - Calmettes [Marseille], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Cholet, CHD Vendée - Hôpital Les Oudairies [La Roche sur Yon], Clinique Mutualiste de l'Estuaire Cité Sanitaire [Saint Nazaire], Bernardo, Elizabeth, Université de Lille-UNICANCER, and Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée)

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Genotype, Leucovorin, Phases of clinical research, Cetuximab, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pharmacology, Irinotecan, Gastroenterology, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Pharmacokinetics, Internal medicine, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Glucuronosyltransferase, Precision Medicine, Aged, business.industry, Hematology, DPD, Middle Aged, 3. Good health, Regimen, 030104 developmental biology, Oncology, Dose intensification, 030220 oncology & carcinogenesis, Pharmacodynamics, FOLFIRI, Dihydropyrimidine deshydrogenase, 5-Fluorouracil dose adaptation, Camptothecin, Female, Fluorouracil, business, Pharmacogenetics, medicine.drug
Abstract

International audience; We conducted a multicenter proof of concept phase II trial in patients with advanced colorectal cancer receiving FOLFIRI-cetuximab regimens to explore individual drug tailoring using pharmacogenetics and pharmacokinetics (PK) monitoring. Patients were stratified by their pharmacogenetic/phenotypic status: the irinotecan dose was adjusted according to the number of TA tandem repeats in the UGT1A1 promoter, while the 5-fluorouracil (5-FU) dose was initially adjusted according to dihydropyrimidine dehydrogenase (DPD) activity at initial screening (5-FU[ODPM Tox]) followed by PK-guided dose optimization (5-FU[ODPM Protocol]). An advanced cetuximab PK/pharmacodynamics (PD) study was performed but dosage remained unchanged. Eighty-five patients receiving second-line chemotherapy were enrolled. Mean irinotecan doses at 3 months were 247 ± 50, 210 ± 53 and 140 ± 21 mg/m[2] for those with 6/6 (33), 6/7 (26), and 7/7 (7) TATA repeats in the UGT1A1 promoter region, respectively. The 5-FU dose was initially reduced in four patients with DPD deficiency, but mean 5-FU dose at 3 months was 2,412 ± 364 mg/m2 (1,615-3,170 mg/m[2]). Grade 4 toxicities were not encountered and grade 4 neutropenia occurred in 6.8%, 5.9%, and 0% of patients with 6/6, 6/7, and 7/7 UGT1A1 genotypes. The objective response rate was 25.8% among the 85 patients, 57.3% in patients with tumors wild type (WT) for KRAS, and 25% in those whose tumor harbored a mutant-KRAS. Secondary resection of hepatic metastases was performed in 31.7% of patients. Median progression-free survival (PFS) for all 85 patients was 181 days and 200, 132, and 121 days for patients with 6/6, 6/7, and 7/7 UGT1A1 genotypes, respectively; these differences were not statistically different. In parallel, a strong relationship was shown between cetuximab AUC and regimen efficacy. We conclude that personalized drug tailoring when administering in FOLFIRI + cetuximab allows for safe and efficient individual dose intensification.

Published
2017

36. Microscopic Colitis or Functional Bowel Disease With Diarrhea: A French Prospective Multicenter Study

Author

Bruno Lesgourgues, C Locher, Alexandre Pariente, Stéphanie de Montigny-Lehnardt, Georges Barjonet, Max Pierre Nicolas, René-Louis Vitte, Stéphane Nahon, Antoine Fleury, Guy Bellaiche, Anne Courillon-Mallet, Gilles Macaigne, Jean-Michel Ghilain, Roger Faroux, Pierre Lahmek, Laurent Costes, and Bénédicte Lambaré

Subjects
Adult, Colitis, Lymphocytic, Diarrhea, Male, medicine.medical_specialty, Time Factors, Colon, Biopsy, Colitis, Collagenous, Colonoscopy, Hypokalemia, Gastroenterology, Autoimmune Diseases, Irritable Bowel Syndrome, Microscopic colitis, Internal medicine, Weight Loss, medicine, Humans, Prospective Studies, Colitis, Defecation, Prospective cohort study, Aged, Hepatology, medicine.diagnostic_test, business.industry, digestive, oral, and skin physiology, Age Factors, Case-control study, Middle Aged, medicine.disease, digestive system diseases, Abdominal Pain, Case-Control Studies, Female, France, medicine.symptom, business
Abstract

To describe the characteristics of a cohort of patients with microscopic colitis (MC; lymphocytic (LC) or collagenous (CC) colitis) and to compare them with patients with functional bowel disorder with diarrhea (FBD-D).Between September 2010 and June 2012, patients fulfilling the following inclusion criteria were prospectively included in 26 centers in France: (i) having at least three bowel movements daily with change in stool consistency; (ii) duration of abnormal bowel habit4 weeks; and (iii) normal or near-normal colonoscopy. Each patient underwent a colonoscopy and colonic biopsies. We compared the demographic, clinical, biological, and etiological characteristic of patients with MC (CC and LC) with those of control patients with FBD-D.A total of 433 patients were included: 129 with MC (87 LC and 42 CC), 23 with another organic disease, and 278 with FDB-D, including patients with diarrhea and abdominal pain who met the criteria of Rome III (irritable bowel syndrome with diarrhea) and patients with functional diarrhea without abdominal pain. Logistic regression analysis identified the following independent predictors of MC: age50 years (odds ratio (OR)=3.1, 95% confidence interval (CI)=1.6-5.9), presence of nocturnal stools (OR=2, 95% CI=1.1-3.9), weight loss (OR=2.5, 95% CI=1.3-4.7), duration of diarrhea12 months (OR=2.0, 95% CI=1.1-3.5), recent introduction of new drugs (OR=3.7, 95% CI=2.1-6.6; P0.0001), and the presence of a known autoimmune disorder (OR=5.5, 95% CI=2.5-12).Age50 years, the presence of nocturnal stools, weight loss, the introduction of a new drug, and the presence of a known autoimmune disease increase the probability of MC and thus the indication for colonoscopy with biopsies.

Published
2014

38. Analysis of circulating tumour DNA (ctDNA) from patients enrolled in the IDEA-FRANCE phase III trial: Prognostic and predictive value for adjuvant treatment duration

Author

May Mabro, C. Lepere, A. de Gramont, Christophe Borg, T. Andre, O. Bouche, C. Louvet, Dewi Vernerey, Pierre Laurent-Puig, Julien Taieb, Joëlle Egreteau, Marc Ychou, Valérie Taly, Claire Mulot, Jérôme Desramé, J. Bennouna, Roger Faroux, Gael Deplanque, L. Mineur, and Camille Bourreau

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Colorectal cancer, business.industry, medicine.medical_treatment, Perforation (oil well), Cancer, Hematology, medicine.disease, Minimal residual disease, Oxaliplatin, Clinical trial, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, T-stage, business, Adjuvant, medicine.drug
Abstract

Background ctDNA has been recently suggested as a major prognostic factor in resected stage II and III colon cancer patients (pts)1,2. Its predictive value for adjuvant treatment intensity or duration is currently unknown. We have analyzed here ctDNA from pts enrolled in the IDEA-FRANCE trial3, its prognostic value and its predictive value for treatment duration (3 or 6 months). Methods ctDNA was tested by using the detection of 2 methylated markers (WIF1 and NPY) by digital droplet PCR accordingly to a method developed and validated for colorectal cancer 4-6. Comparisons for pts and tumour characteristics and DFS will be done between the ctDNA tested pts and the full study population and between ctDNA positive and negative pts. DFS has been analyzed in the 6 and 3M treatment arms according to ctDNA results. Subgroup analyses for high- and low-risk pts were pre-planned. Results Of the 1345/2010 pts that consented to the IDEA translational research program, with available blood sample for ctDNA testing, 805 have been sampled before chemotherapy start and fully analyzed. More PS 0 (77% vs 71%) and more T4 and/or N2 (28% vs 23%) were observed in the 805 pts studied here than in the 1205 pts left. 696 pts were found ctDNA- and 109 ctDNA + (13.5%). ctDNA+ pts were more often T4, poorly differentiated and with tumour perforation. 2-year DFS was 64% vs 82% in ctDNA+ and – pts, respectively (HR :1.75 (95%CI 1.25-2.45) p = 0.001). In multivariate analysis including Age, Gender, MSI, perforation, T stage, N stage and treatment arm, ctDNA was confirmed as an independent prognostic marker (adj.HR: 1.85 (95%CI 1.31 to 2.61) p Conclusions In this first ctDNA assessment on a large series coming from a phase III clinical trial we found 13.5% of pts with ctDNA post-surgery. ctDNA was confirmed as an independent prognostic marker. In this series, 6 months of treatment seems better in both ctDNA+ and- pts. [1]Tie J, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.Sci Transl Med. 2016 Jul 6;8(346):346ra92. [2]Scholer LV, et al. Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer. Clin Cancer Res. 2017 Sep 15;23(18):5437-5445. [3] Andre T, et al.Three Versus 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Patients With Stage III Colon Cancer: Disease-Free Survival Results From a Randomized, Open-Label, International Duration Evaluation of Adjuvant (IDEA) France, phase III Trial.J Clin Oncol. 2018 May 20;36(15):1469-1477. [4] Garrigou S, et al. A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker. Clin Chem. 2016;62:1129-1139. [5] Garlan F, et al. Early Evaluation of Circulating Tumor DNA as Marker of Therapeutic Efficacy in Metastatic Colorectal Cancer Patients (PLACOL Study). Clin Cancer Res.2017;23:5416-5425. [6] Bachet JB, et al. RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study. Ann Oncol. 2018May 1;29(5):1211-1219. Clinical trial identification NCT00958737. Legal entity responsible for the study Gercor-Prodige. Funding Clinical trial: INCa, GERCOR; Translational project: ARC (Association de Recherche contre le Cancer, Paris, France). Disclosure J. Taieb: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: pierre fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi. D. Vernerey: Honoraria (self), Advisory / Consultancy: HalioDX; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Janssen. J. Bennouna: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Published
2019

39. Nal-iri/lv5-fu versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI-PRODIGE 62): A FFCD multicenter, randomized, phase II study

Author

L. Gaba, Violaine Randrian, Sylvain Manfredi, Laetitia Dahan, Roger Faroux, L. Mineur, F. Di Fiore, Astrid Lièvre, Gilles Breysacher, A. Lopez, Guillaume Roquin, C. Louvet, Emilie Barbier, J.-P. Metges, Samy Louafi, Christophe Borg, Jérôme Desramé, David Tougeron, Pierre Laurent-Puig, and Antoine Adenis

Subjects
Oncology, medicine.medical_specialty, Performance status, business.industry, Hematology, Chemotherapy regimen, law.invention, Irinotecan, Randomized controlled trial, law, Internal medicine, medicine, FOLFIRI, Progression-free survival, Lost to follow-up, business, Survival rate, medicine.drug
Abstract

Background Half of patients newly diagnosed with esophagus squamous cell cancer (ESCC) has a metastatic ESCC (mESCC) and half of patients with initial loco-regional disease presents disease recurrence after surgery and/or chemoradiation. Although not validated by a phase III trial, first-line palliative chemotherapy combines fluoropyrimidine with platinum salt. Patients with disease progression after platinum-based chemotherapy and good performance status may benefit from a second-line chemotherapy. Based on phase I/II trials or retrospective studies, the most commonly used regimens in second-line setting of mESCC are paclitaxel monotherapy or irinotecan monotherapy or combined with 5FU (FOLFIRI). Up to now, there is no randomized trial available. Trial design OESIRI is a multicenter, open-label, randomized phase II trial designed to evaluate efficacy and safety of nanoliposomal irinotecan (NalIRI) plus 5FU versus paclitaxel as second-line therapy in mESCC. Main inclusion criteria are histologically proven mESCC after failure of first-line platinum-based chemotherapy and WHO performance status ≤ 2. Patients initially treated by surgery and chemotherapy or definitive chemoradiation are eligible if relapse occurred less than 6 months after the end of the treatment. In the experimental arm, patients will receive, every 14 days, intravenous (IV) infusion of NalIRI (80 mg/m2) followed by 5FU (2400 mg/m2 over 46 h). In the control arm, patients will receive at days 1, 8 and 14 of a 28 days-cycle, an IV infusion of paclitaxel (80 mg/m2). The primary objective is to evaluate the percentage of patients alive 9 months after randomisation. The clinical hypotheses are to extent the 9-months survival rate from 40% to 60%. With a one-sided type one error α of 5%, a power of 85%, a 5% rate of patients lost to follow-up, 53 patients per arm (n = 106) will be randomized. Secondary endpoints are progression-free survival, overall survival, response rate, safety and quality of life. Circulating tumor DNA will be monitored to assess its predictive value of response to treatment. Inclusions started in January 2019 and theoretical end of recruitment is January 2022. Legal entity responsible for the study Federation Francaise de Cancerologie Digestive. Funding Servier. Disclosure All authors have declared no conflicts of interest.

Published
2019

40. Adjuvant chemotherapy versus perioperative chemotherapy (CTx) for resectable gastric signet ring cell (SRC) gastric cancer: A multicenter, randomized phase II study (PRODIGE 19)

Author

Roger Faroux, May Mabro, Sylvain Manfredi, Frédéric Di Fiore, Nicolas Barriere, David Malka, Anne Thirot Bidault, Clarisse Eveno, François Mauvais, Meher Ben Abdelghani, Vincent Hautefeuille, Nicolas Carrere, Joëlle Egreteau, Bernard Meunier, Olivier Bouché, Guillaume Piessen, Antoine Adenis, Karine Le Malicot, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital universitaire Robert Debré [Reims], Fédération Francophone de la Cancérologie Digestive, FFCD, CHU Amiens-Picardie, Centre Hospitalier Départemental Les Oudairies, Groupe Hospitalier Bretagne Sud (GHBS), CHU Pontchaillou [Rennes], Hôpital Foch [Suresnes], Département de chirurgie digestive, [CHU Toulouse], Centre d'étude spatiale des rayonnements (CESR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Université Fédérale Toulouse Midi-Pyrénées-Météo-France -Institut de Recherche pour le Développement (IRD)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Centre Paul Strauss, CRLCC Paul Strauss, Chirurgie digestive [CHU Amiens], Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Université de Picardie Jules Verne (UPJV), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Lille, Service Chirurgie viscérale et digestive [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen], CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, Adjuvant chemotherapy, business.industry, Signet ring cell, [SDV]Life Sciences [q-bio], Incidence (epidemiology), medicine.medical_treatment, education, Phases of clinical research, Cancer, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Perioperative chemotherapy, Internal medicine, medicine, business, 030215 immunology, Proto-oncogene tyrosine-protein kinase Src
Abstract

4019 Background: The incidence of SRC gastric cancers is markedly increasing in Western countries. SRC cancers may harbor intrinsic resistance to chemotherapy (CTx) leaving many clinicians unsure of the benefits of delaying surgery to pursue a neoadjuvant approach. The primary objective of this study was to assess whether upfront surgery plus adjuvant CTx would provide enough survival benefit for study in a phase III trial when compared to perioperative CTx. Methods: Patients with stage IB-III SRC gastric cancer were randomly assigned to receive upfront surgery plus adjuvant CTx (epirubicin, cisplatin and 5-fluorouracil [ECF regimen], 6 cycles; experimental arm [SurgFirst]) or perioperative CTx (ECF, 3 cycles before and 3 cycles after surgery; control arm [CTxFirst]). Randomization (1:1) was stratified by tumor stage, tumor location, performance status and center. The primary endpoint was overall survival (OS) at 2 years (OS2; target (H1): OS2 > 26%). Results: 83 eligible patients were included in 27 centers from 11/12 to 09/16 (median age, 61 years (range: 32-80 years); male, 59%; ECOG PS 0-1, 99%). Results were (CTxFirst/SurgFirst): full completion of CTx, 87%/77%; surgical resection, 82.5%/90%; major postoperative complications (Clavien Dindo III-IV), 24%/23%; R0 resection rate, 88%/78%; OS2, 60%/53.5%; and median OS, 39/28 months (exploratory hazard ratio, 0.71 [95%CI: 0.40-2.64]). Conclusions: This trial met its primary endpoint (OS2 > 26% in the experimental arm). With OS2 rates > 50%, both CTx modalities deserve further evaluation in Phase III studies in stage IB-III SRC gastric cancer. Clinical trial information: NCT01717924.

Published
2019

41. Validation of the Immunoscore prognostic value in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France cohort study (PRODIGE-GERCOR)

Author

Alex Duval, Thierry André, Christophe Borg, Julien Taieb, Jean-François Emile, Christophe Louvet, Jérôme Galon, Magali Svrcek, Franck Pagès, Aurelie Catteau, Laurent Mineur, Dewi Vernerey, Roger Faroux, Jérôme Desramé, Fabienne Hermitte, Jaafar Bennouna, Julie Henriques, Pierre Laurent-Puig, Rim Ben Jannet, and Florence Marliot

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, business.industry, medicine.disease, Stage III Colon Cancer, Oxaliplatin, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Stage (cooking), business, Value (mathematics), 030215 immunology, medicine.drug, Cohort study
Abstract

3513 Background: The Immunoscore (IS), which has been shown to prognostically classify Stage I-III colon cancer (CC) patients, was assessed in the IDEA France cohort study evaluating 3 versus 6 months of oxaliplatin-based adjuvant chemotherapy in Stage III CC patients. Methods: Densities of CD3+ and cytotoxic CD8+ T cells in the tumor and invasive margin of each patient were quantified by digital pathology and converted to IS using pre-defined published cut-off. The performance of IS to predict disease-free survival (DFS) was assessed in the modified intention-to-treat population, in each study arm, and was adjusted with relevant clinical features in multivariable Cox models. Harrell’s C-statistics was used to investigate the IS performance. Results: 1322 patients were included; 82 were excluded due to pre-analytical non-conformity. IS was successfully analyzed in 1062 (85.6%) eligible patients. In a 2-category IS analysis, Low and (Int+High) IS were observed in n=599 (43.6%) and n=463 (56.4%) patients, respectively. IS was significantly correlated with T stage, T/N stage (T1-3 and N1 versus T4 and/or N2), and microsatellite instability status. The study met its primary objective of validating that Low IS identifies patients with higher-risk of relapse or death [HR=1.54; 95%CI 1.24-1.93, p=0.0001]. The 3-year DFS rates were 66.80% [95%CI 62.23-70.95] and 77.14% [95%CI 73.50-80.35] for Low IS and (Int+High) IS, respectively. In multivariable analysis, IS remained independently associated with DFS (p

Published
2019

42. Screening patients for fluoropyrimidine-related toxicity risk

Author

Jean-Philippe Metges, Tamara Matysiak-Budnik, Roger Faroux, Marc Ferec, Nadege Blouin, Hélène Senellart, Mario Campone, Michèle Boisdron-Celle, Valérie Rossi, Valérie Seegers, Claire Stampfli, Jonathan Dauve, and Olivier Capitain

Subjects
Cancer Research, medicine.medical_specialty, Chemotherapy, Oncology, business.industry, Public health, medicine.medical_treatment, Toxicity, medicine, Intensive care medicine, business
Abstract

3529 Background: Severe, sometimes fatal, toxicity can occur during the 1st or 2nd course of chemotherapy using fluoropyrimidines (FPs), and poses a serious public health problem. FPs carry a 3-5% risk of grade ≥ 3 early toxicities and 0.2% risk of death linked to Dihydropyrimidine Dehydrogenase (DPD) deficiency. Methods: Of 29,000 patients screened since July 2000, 472 were referred to us due to severe toxicity during 1st round 5-FU, or because pre-screening was done too late. Toxicity evaluation was performed according to the NCI scale of adverse reactions to cancer drugs (0=none, 5=death). Patients were previously 5-FU naïve, had different cancers, and received various protocols, eg. 5FU or Capecitabine; bolus±continuous or per os. The reliability of the following 4 pre-treatment screening tests to predict grade≥ 4 toxicity was assessed: 1) DPYD genotype mutation (*2A,*2B,*7, 13, HapB3) 2) Plasma uracil (U) level, 3) Plasma dihydrouracil/uracil ratio (UH2/U) 4) a multiparametric approach with genotyping, UH2/U ratio and key patient factors (age, sex, etc.). McNemar’s test with Bonferroni correction was used for statistical analysis. Results: Of the 472 referred patients, 169 had grade 4 or 5 toxicity, of which 41 died from toxicity. 98 had one or plus DPYD mutation: 42(42.9%)*2A; 43(43.9%)*2B; 3(3%)*7; 4(4%)*13; 8(8.16%) HapB3; 1 was homozygous *2A. Data below compare the 4 screening methods for predicting grade 4-5 toxicity. Conclusions: The multiparametric approach is statistically (p

Published
2019

43. Effect of 5 years of imaging and CEA follow-up to detect recurrence of colorectal cancer: The FFCD PRODIGE 13 randomised phase III trial

Author

Philippe Deguiral, Roger Faroux, Sylvain Manfredi, Laurent Cany, Côme Lepage, Olivier Bouché, Antoine Adenis, Laurent Bedenne, M. Baconnier, Jean-Marc Phelip, Jean-Francois Ain, Denis Pezet, Eric Terrebone, and Karine Le Malicot

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Adenoma, Colorectal cancer, Colonoscopy, Clinical Protocols, Internal medicine, medicine, Carcinoma, Humans, Prospective Studies, Stage (cooking), Prospective cohort study, Early Detection of Cancer, Survival analysis, Aged, Ultrasonography, Aged, 80 and over, Hepatology, medicine.diagnostic_test, business.industry, General surgery, Gastroenterology, Middle Aged, medicine.disease, Survival Analysis, Carcinoembryonic Antigen, Intention to Treat Analysis, Dysplasia, Female, Neoplasm Recurrence, Local, Colorectal Neoplasms, Tomography, X-Ray Computed, business, Follow-Up Studies
Abstract

Colorectal cancer (CRC), the most common digestive cancer in rance, is a major public health problem. There are an estimated 0,000 new cases every year and 200,000 prevalent cases [1]. Its ncidence has increased by more than 50% over the past 20 years 24,000 new cases/year in 1980, 36,600 in 2000). On the other and, over the same period, the number of deaths has remained table (16,000 deaths in 2000), which reflects a major therapeutic rogress [2,3]. Around 75% of patients may benefit from surgical resection ith curative intent [4]. Among them, nearly 30% stage II and over 5% stage III patients present a loco-regional or distant recurrence r a metachronous cancer within 5 years of initial treatment [5]. his high risk of recurrence raises the question of postoperative onitoring in order to detect early recurrences and metachronous ancers at a curable stage. The annual incidence of adenomas is between 3 and 5%, and the umulative risk of metachronous cancer is 2% at 5 years and 7% t 20 years. Endoluminal recurrences and metachronous cancers re rare, therefore intensive endoscopic monitoring is not useful 5,6]. After resection of CRC, the French national thesaurus of good ractices in digestive cancer (TNCD) [7] recommends a colonoscopy ithin 6 months after surgery (if incomplete or of poor quality efore surgery), followed by another at 3 years and then every 5 ears in case of normal results. After excision of more than 3 adeomas or of one at-risk adenoma (size > 1 cm, villous contingent, igh grade dysplasia or in situ carcinoma), the first colonoscopy is erformed after 1 year.

Published
2015

44. Prognostic factor analysis for elderly patients treated for metastatic colorectal cancer in the randomized phase II trial PRODIGE 20

Author

F. Retornaz, Julien Taieb, E. Francois, S. Kirscher, Thomas Aparicio, Thierry Lecomte, O. Bouche, F. Khemissa Akouz, Dominique Genet, Alice Oden-Gangloff, Laurent Bedenne, F. El Hajbi, Sandrine Lavau-Denes, Elena Paillaud, M. Baconnier, Christophe Locher, E. Maillard, P.L. Etienne, Roger Faroux, Y. Rinaldi, Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Fédération Francophone de la Cancérologie Digestive, FFCD, Institut Sainte Catherine [Avignon], Service de gastroenterologie [CHU Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Hôpital Privé des Côtes d'Armor ( HPCA ), Centre Hospitalier Départemental Les Oudairies, Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, CRLCC Oscar Lambret, Centre Hospitalier de Meaux, Hôpital Européen [Fondation Ambroise Paré - Marseille], CHU Trousseau [Tours], CHRU Tours, CHU Limoges, CH Annecy, Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, CHU Rouen, Polyclinique de Limoges - site François Chénieux [Limoges], Unité de médecine gériatrique ( Gériatrie - Henri Mondor ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Programme Hospitalier de Recherche Clinique, Laboratoires Roche, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Privé des Côtes d'Armor (HPCA), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Normandie Université (NU), Unité de médecine gériatrique (Gériatrie - Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Université de Lille-UNICANCER

Subjects
0301 basic medicine, Oncology, Prognostic factor, medicine.medical_specialty, Colorectal cancer, business.industry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, medicine.disease, 3. Good health, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

45. Effect of 5 years of imaging and CEA follow-up to detect recurrence of colorectal cancer - PRODIGE 13 a FFCD and Unicancer phase III trial: baseline characteristics

Author

E. Maillard, D. Pere-Verge, T. Chatellier, Côme Lepage, J. Ezenfis, J.-C. Duchmann, Antoine Adenis, Gilles Breysacher, Astrid Lièvre, M. Ben Abdelghani, Roger Faroux, Ariane Darut-Jouve, Y. Rinaldi, M. Duluc, J.M. Phelip, O. Bouche, A. Pelaquier, D. Pillon, P. Geoffroy, L. Cany, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHU Saint-Etienne, Polyclinique Francheville, Fédération Francophone de la Cancérologie Digestive, FFCD, Pontchaillou. Service des maladies de l'appareil digestif, Centre Hospitalier Universitaire de Rennes, Centre Hospitalier Départemental Les Oudairies, Centre Hospitalier de Compiègne, CHU, Service d'oncologie médicale [CHU Strasbourg], CHU Strasbourg, Hôpitaux Civils Colmar, Institut de Chimie de Strasbourg, Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ), Centre hospitalier Saint Joseph - Saint Luc [Lyon], CH Montélimar, Centre Hospitalier Fleyriat [Bourg en Bresse], Clinique Drévon, Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Center Oscar Lambret, CRLCC Oscar Lambret, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service des Maladies de l'Appareil Digestif [CHU Rennes], CHU Pontchaillou [Rennes], Service gastro-entérologie et hépatologie, Centre Hospitalier Compiègne-Noyon, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire [Rennes], and Université Lille Nord de France (COMUE)-UNICANCER

Subjects
Oncology, medicine.medical_specialty, business.industry, Colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Stage ii, medicine.disease, Gastrointestinal tumours, 3. Good health, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, Pulmonary imaging, Internal medicine, Radiological weapon, Baseline characteristics, medicine, 030212 general & internal medicine, business, 030217 neurology & neurosurgery, Colorectal
Abstract

International audience; Background: PRODIGE 13 is a cooperative prospective multicentre controlled phase III trial evaluating by double randomisation the impact of intensive radiological monitoring versus a standard one and CEA monitoring versus no monitoring in Stage II or III colorectal cancer. This abstract describes patient's baseline characteristics.Methods: Recommendations for colorectal cancer, according to various scientific societies have been based on heterogeneous clinical trials, and indeed mainly on expert opinions. Differences still exist particularly concerning the imaging techniques used. The CEA dosage is also poorly evaluated. Despite their limits, recent trials suggest that survival is increased thanks to clinical monitoring combined with hepatic and pulmonary imaging and possibly CEA assay. PRODIGE 13 is a large randomised trial of monitoring strategy and will evaluate the strategies to...

Published
2016

46. P-136Evolution of efficacy and safety of cetuximab with the determination of RAS status in Metastatic Colorectal Cancer (mCRC) elderly patients

Author

E. Achour Nacr, Roger Faroux, A. Gorlaouen, Olivier Capitain, L. Etienne Pierre, Fanny Marhuenda, Isabelle Cumin, J.-F. Bouret, J.-Y. Douillard, F. Ramée Jean, Philippe Deguiral, M.-A. Coulon, Olivier Dupuis, D. Deniel Lagadec, L. Raoul Jean, A. Le Rol, F. Grude, and J.-P. Metges

Subjects
Oncology, medicine.medical_specialty, Cetuximab, Colorectal cancer, business.industry, Hematology, medicine.disease, Abstracts, Text mining, Internal medicine, medicine, business, medicine.drug
Published
2016

47. Geriatric factors analyses from FFCD 2001-02 phase III study of first-line chemotherapy for elderly metastatic colorectal cancer patients

Author

Faiza Khemissa, Jean-François Seitz, J. Cretin, Olivier Bouché, Laurent Teillet, Dominique Genet, Jean-Baptiste Bachet, Jean-Louis Jouve, Olivier Boulat, Dany Gargot, Thierry Lecomte, Céline Lepère, Mohamed Ramdani, Gilles Breysacher, Christophe Locher, Iradj Sobhani, Emilie Maillard, Emmanuel Mitry, Thomas Aparicio, Dominique Auby, Roger Faroux, Mohamed Gasmi, Laetitia Stefani, Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération Francophone de la Cancérologie Digestive, FFCD, CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpitaux Civils Colmar, Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Service Hépato-gastroentérologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département de Médecine, Centre Hospitalier Libourne, Centre Hospitalier Départemental Les Oudairies, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut Curie [Paris], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre hospitalier de Libourne, Service de gastroentérologie et cancérologie digestive [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de gastro-entérologie - Hôpital Henri Mondor, Institut Curie, Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Image et ville ( IV ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Oncology, Male, Cancer Research, medicine.medical_specialty, Multivariate analysis, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Prognostic factors, Irinotecan, Disease-Free Survival, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Elderly, Quality of life, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Karnofsky Performance Status, Neoplasm Metastasis, Prospective cohort study, Geriatric Assessment, Aged, Aged, 80 and over, Chemotherapy, biology, business.industry, medicine.disease, 3. Good health, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, biology.protein, Quality of Life, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract

IF 6.163; International audience; AIM:Several predictors of metastatic colorectal cancer (mCRC) outcomes have been described. Specific geriatric characteristics could be of interest to determine prognosis.METHOD:Elderly patients (75+) with previously untreated mCRC were randomly assigned to receive infusional 5-fluorouracil-based chemotherapy, either alone (FU) or in combination with irinotecan (IRI). Geriatric evaluations were included as an optional procedure. The predictive value of geriatric parameters was determined for the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).RESULTS:From June 2003 to May 2010, the FFCD 2001-02 randomised trial enrolled 282 patients. A baseline geriatric evaluation was done in 123 patients; 62 allocated to the FU arm and 61 to the IRI arm. The baseline Charlson index was ≤1 in 75%, Mini-Mental State Examination was ≤27/30 in 31%, Geriatric Depression Scale was >2 in 10% and Instrumental Activities of Daily Living (IADL) was impaired in 34% of the patients. Multivariate analyses revealed that no geriatric parameter was predictive for ORR or PFS. Normal IADL was independently associated with better OS. The benefit of doublet chemotherapy on PFS differed in subgroups of patients ≤80 years, with unresected primary tumour, leucocytes >11,000 mm3 and carcinoembryonic antigen >2N. There was a trend towards better OS in patients with normal IADL.CONCLUSION:The autonomy score was an independent predictor for OS. A trend toward a better efficacy of doublet chemotherapy in some subgroups of patients was reported and should be further explored.

Published
2016

48. DPYD Genotyping to Predict Adverse Events Following Treatment With Flourouracil-Based Adjuvant Chemotherapy in Patients With Stage III Colon Cancer:A Secondary Analysis of the PETACC-8 Randomized Clinical Trial

Author

Julien Taieb, Pieter Jan Cuyle, Mette Karen Yilmaz, Roger Faroux, Ramon Salazar, Axel Matzdorff, Pierre Laurent-Puig, Marc Vincent, Richard Greil, Karine Le Malicot, Stefania Landolfi, Côme Lepage, Philippe Alexandre, Sabine Tejpar, and Valérie Boige

Subjects
Oncology, Cancer Research, medicine.medical_specialty, business.industry, Colorectal cancer, Phases of clinical research, Combination chemotherapy, Odds ratio, medicine.disease, 030226 pharmacology & pharmacy, 3. Good health, Surgery, Oxaliplatin, 03 medical and health sciences, Regimen, 0302 clinical medicine, Fluorouracil, 030220 oncology & carcinogenesis, Internal medicine, medicine, DPYD, business, medicine.drug
Abstract

Importance: Previous pharmacogenetic studies have shown the prognostic impact of several rare dihydropyrimidine dehydrogenase gene (DPYD) variants on fluorouracil-related adverse events (fluorouracil AEs). However, conflicting results highlight the need for prospective validation in large, homogeneous patient populations uniformly treated with current standard combination therapies used in colon cancer (CC).Objective: To determine the impact of DPYD variants on fluorouracil AEs in patients with stage III CC treated with a fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) regimen.Design, Setting, and Participants: Pharmacogenetic substudy of 1545 patients who participated from December 2005 to November 2009 in the European Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 randomized phase 3 clinical trial.Interventions: Patients with resected stage III CC were randomized to receive standard adjuvant FOLFOX4 alone or FOLFOX4 combined with cetuximab for 6 months.Main Outcomes and Measures: Patients were genotyped on 25 DPYD variants. We tested the individual associations between each DPYD variant and grade 3 or greater fluorouracil AEs.Results: A total of 1545 patients (57.6% male; median [range] age, 60 [19-75] years) were included in the analysis. The incidence of grade 3 or greater fluorouracil AEs in D949V and V732I (DPYD*6) carriers was 18 in 21 (85.7%) and 121 in 199 (60.8%), respectively. After adjusting for multiple variables, statistically significant associations were identified between grade 3 or greater fluorouracil AEs and both D949V (odds ratio [OR], 6.3 [95% CI, 2.0-27.0]; P Conclusions and Relevance: In this large phase 3 study, statistically significant associations were found between DPYD variants (D949V and V732I) and increased incidence of grade 3 or greater fluorouracil AEs in patients treated with adjuvant fluorouracil-based combination chemotherapy. Further studies are warranted to confirm and quantitate these associations.Trial Registration: eudract Identifier 2005-003463-23.

Published
2016

49. The Periscreen Strip Is Highly Efficient for the Exclusion of Spontaneous Bacterial Peritonitis in Cirrhotic Outpatients

Author

Alexandre Louvet, Olivier Roux, Matthieu Schnee, Arnaud Pauwels, L. Elkrief, Marie Angèle Robic, Thong Dao, Eric Nguyen-Khac, Brigitte Bernard-Chabert, Jean-Baptiste Nousbaum, Si Ahmed Si Nafa, Vincent Macé, Delphine Weil, Vincent Di Martino, Valéry-Pierre Riche, Mourad Medmoun, Rodolphe Anty, Caroline Jezequel, Roger Faroux, Alexandra Heurgué-Berlot, Aurélie Le Thuaut, Nicolas Carbonell, Florence Tanné, Mehdi Kaassis, Edouard Bardou-Jacquet, Karim Aziz, Ghassan Riachi, Denis Grasset, Jean-Paul Cervoni, Thierry Thevenot, Sofia Hermann, Isabelle Ollivier-Hourmand, Christophe Bureau, Gérard Thiéfin, Hortensia Lison, Angh Cfehtp, Yasmina Belouchrani, Thomas Mouillot, Clémence M. Canivet, Charline Briot, H. Labadie, Jean-François Cadranel, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Group Hospitalier public Sud Oise GHPSO (Creil), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital universitaire Robert Debré [Reims], CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service des Maladies de l'Appareil Digestif, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier de Gonesse, Service d’Hépato-Gastroentérologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Département Digestif, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital de l'Archet, Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bordeaux (UB), Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Méthodes Formelles pour la Bioinformatique (MéForBio), Laboratoire des Sciences du Numérique de Nantes (LS2N), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Service d'hépato-gastroentérologie, Centre Hospitalier Laennec de Creil, Service de gastroentérologie (CHD Vendee - Hopital Les Oudairies, La Roche Sur Yon), CHD Vendee (La Roche Sur Yon), Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France, affiliation inconnue, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT), Service des Maladies de l'Appareil Digestif [CHU Rennes], CHU Pontchaillou [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre Hospitalier de Saint-Denis [Ile-de-France], Service d'Hépato-Gastro-Entérologie (CHU de Dijon), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)

Subjects
Liver Cirrhosis, Male, medicine.medical_specialty, Neutrophils, [SDV]Life Sciences [q-bio], Peritonitis, Sensitivity and Specificity, Gastroenterology, Leukocyte Count, 03 medical and health sciences, 0302 clinical medicine, Spontaneous bacterial peritonitis, Predictive Value of Tests, Internal medicine, Ambulatory Care, medicine, Ascitic Fluid, Humans, Paracentesis, Prospective Studies, Aged, Hepatology, business.industry, Ascites, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Bacterial Infections, Middle Aged, medicine.disease, Logistic Models, 030220 oncology & carcinogenesis, Multivariate Analysis, Leukocytes, Mononuclear, Colorimetry, Female, 030211 gastroenterology & hepatology, business
Abstract

International audience; OBJECTIVES: We aimed to assess the performance of a new strip (Periscreen) for the rapid diagnosis of spontaneous bacterial peritonitis (SBP). METHODS: Ascitic fluid (AF) of cirrhotic patients hospitalized between March 2014 and August 2015 was independently tested by two readers using the new strip, which has four colorimetric graduations (negative, trace, small, and large). SBP was diagnosed on neutrophils in ascites>250/mm(3). Ascites not related to portal hypertension were excluded. RESULTS: Overall, 649 patients from 21 French centers were included and 1,402 AF (803 AF samples from 315 outpatients and 599 samples from 334 inpatients) were assessed. Eighty-four AF samples (17 AF in 9 outpatients and 67 AF in 31 inpatients) were diagnosed as SBP. The prevalence of SBP was 6% (2.1% in outpatients vs. 11.2% in inpatients; P

Published
2016

50. Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001–02)

Author

Gilles Breysacher, F. Masskouri, C. Choine, François Morvan, Pascal Hammel, Jean-François Seitz, P. Amoyal, J. Cretin, G. Gatineau-Sailliant, Christophe Locher, Thomas Aparicio, G. Bordes, O. Boulat, David Tougeron, I. Cumin, O. Berthelet, Anne Thirot Bidault, M. Pauwels, X. Moncoucy, Faiza Khemissa, F. Petit-Laurent, X. Adhoute, P. Prost, J.P. Lagasse, Jean-Louis Legoux, J. Ezenfis, N. Le Provost, Pierre Michel, A. Gueye, P. Pouderoux, G. Le Pessec, Julien Taieb, B. Landi, H. Fattouh, A. Azzedine, Mohamed Ramdani, Matthieu Schnee, Laurent Bedenne, Jean-Louis Jouve, C. Rebischung, J. Thaury, Ph. Rougier, C. Lobry, F. Guiliani, Jean-Baptiste Bachet, F. Ricard, L. Stefani, R. Mackiewicz, Dominique Genet, E. Cuillerier, C. Bineau, A.M. Queuniet, P. Couzigou, Jean-Marc Phelip, Eveline Boucher, B. Garcia, D. Cleau, M. Schneider, Iradj Sobhani, M. Mozer, Roger Faroux, Mohamed Gasmi, J. Charneau, Côme Lepage, Thierry Lecomte, Céline Lepère, D. Auby, Eric Terrebonne, R. Benoit, Emmanuel Mitry, D. Gargot, J. Martin, M. Baconnier, V. Derias, Achim Weber, Nadia Bouarioua, L. Chone, Catherine Lombard-Bohas, Patrick Texereau, B. Denis, May Mabro, Emilie Maillard, Sandrine Lavau-Denes, F. Di Fiore, C. Girault, J. Provençal, O. Bouche, F. Bonnetain, A. Gagnaire, Service de Gastro-entérologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier de Blois (CHB), Hôpital Nord [CHU - APHM], Centre Hospitalier de Meaux, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de hépato-gastro-entérologie - cancérologie digestive [CH de Perpignan], Centre Hospitalier Saint Jean de Perpignan, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Métropole Savoie [Chambéry], Hôpital pasteur [Colmar], Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Duchenne, CH Boulogne sur Mer, Clinique Bonnefon, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Henri Duffaut (Avignon), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]

Subjects
Oncology, Male, medicine.medical_specialty, Leucovorin, colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Irinotecan, chemotherapy, Gastroenterology, elderly, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Progression-free survival, geriatric oncology, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Hazard ratio, Hematology, Chemotherapy regimen, 3. Good health, Treatment Outcome, Fluorouracil, 030220 oncology & carcinogenesis, Multivariate Analysis, FOLFIRI, 030211 gastroenterology & hepatology, Camptothecin, Female, business, Colorectal Neoplasms, medicine.drug
Abstract

International audience; BACKGROUND:Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients.PATIENTS AND METHODS:Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR).RESULTS:From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%).CONCLUSION:In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2.CLINICALTRIALSGOV:NCT00303771.

Published
2016

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