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1. Predictive value of vascular endothelial growth factor polymorphisms for maintenance bevacizumab efficacy in metastatic colorectal cancer: an ancillary study of the PRODIGE 9 phase III trial

Author

Bernadette de Rauglaudre, Camille Sibertin-Blanc, Aurélie Fabre, Karine Le Malicot, Jaafar Bennouna, François Ghiringhelli, Julien Taïeb, Valérie Boige, Olivier Bouché, Thierry Chatellier, Roger Faroux, Eric François, Stéphane Jacquot, Dominique Genet, Claire Mulot, Sylviane Olschwang, Jean-François Seitz, Thomas Aparicio, and Laetitia Dahan

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: Several studies have reported the impact of single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor ( VEGF ) pathway genes on the efficacy of bevacizumab in metastatic colorectal cancer (mCRC), but results are still inconsistent. The PRODIGE 9 phase III study compared bevacizumab maintenance versus observation alone after induction chemotherapy with FOLFIRI plus bevacizumab. Objective: We evaluated the impact of SNPs of VEGF-A , VEGF receptors ( VEGFR-1, VEGFR-2 ), and hypoxia inducible factor-1α ( HIF-1α ) on tumor control duration (TCD), overall survival (OS), progression-free survival (PFS), and duration of first chemotherapy free-intervals (CFI). Patients and methods: We included 314/491 patients from PRODIGE 9 with a DNA blood sample available. Nine SNPs were genotyped on germline DNA using real-time Polymerase Chain Reaction TaqMan TM (Thermo Fisher Scientific, Waltham, MA , USA 02451). Results: In the bevacizumab arm, patients with the VEGFR-1 rs9582036 CC genotype ( n = 14) had significantly longer TCD [22.4 months (95% confidence interval (CI): 14.75-not reached)] than patients with the AA or CA genotype [14.4 months (95% CI: 11.7–17.1)] ( p = 0.036), whereas there was no significant difference in the observation arm. In the bevacizumab arm, no significant difference was found between the CC, and AA or CA genotype for OS [28.2 (95% CI: 18.1–42.8) versus 22.5 (95% CI: 18.6–24.6) months, p = 0.5], PFS [9.4 (95% CI: 7.2–11.3) versus 9.2 (95% CI: 8.71–10.1)], and duration of the first CFI [4.6 (95% CI: 1.6–13.3) versus 4.14 (95% CI: 0.5–29.0) months, p = 0.3]. Conclusion: Among mCRC patients treated with bevacizumab maintenance, those with the VEGFR-1 rs9582036 CC genotype experienced longer TCD. The presence of this genotype may thus predict a benefit of bevacizumab maintenance in mCRC.

Published
2022
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2. The Characteristics of Diverticular Disease in Caribbean Population: A Control Group Study

Author

Moana Gelu-Simeon, Matthieu Schnee, Marie-Josée Lafrance, Pauline Plazy-Chabrand, Anne-Sophie Schneck, Georgette Saint-Georges, Marceline Alexis, Stéphanie Delumeau, Philippe Montigny, Roger Faroux, Jérome Dimet, and Eric Saillard

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background. Diverticulosis is not well characterized in the Caribbeans. Our aim was to compare the anatomical presentation of colonic diverticulosis in African Caribbeans (group AC) versus Europeans (group E) and severity. Methods. We conducted a prospective controlled study involving 274 patients admitted for lower gastrointestinal haemorrhage (LGIH) in France (center 1: Guadeloupe; center 2: La Roche-sur-Yon); 179 cases with diverticular haemorrhage, including 129 in group AC and 40 in group E. Exploration of the colon included a detailed assessment of diverticula using a dedicated endoscopic grid. Results. AC and E had similar characteristics in terms of age, gender, previous history of LGIH, body mass index, dietary habits, and medications, but AC had significantly poorer hemodynamic parameters at admission and required more blood transfusions (66.7% vs. 42.5%; p=0.01) during hospitalization. Out of the 169 patients included in the study, a complete exploration of the colon was achieved in 81% (N = 137) (AC, n = 106; E, n = 31), and revealed right-side diverticulosis in AC (in 90.6%, included into a pancolonic form in 73.6% vs. 35.5%; p=0.0002) and left-side diverticulosis in E (in 96.8%, isolated form in 58.1% vs. 9.4%, p=0.0002). These data were confirmed by a sensitivity analysis using an endoscopic grid in 92 patients, achieving a higher frequency and larger size of diverticula in AC. Conclusion. Our study has shown that diverticulosis was pancolonic in AC and more frequently associated with more severe haemorrhage than the left-sided diverticulosis of Europeans. This anatomical presentation may be driven by the genetic background more than the environment and diet.

Published
2022
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3. High-Density of FcγRIIIA+ (CD16+) Tumor-Associated Neutrophils in Metastases Improves the Therapeutic Response of Cetuximab in Metastatic Colorectal Cancer Patients, Independently of the HLA-E/CD94-NKG2A Axis

Author

Marie Denis Musquer, Nicolas Jouand, Morgane Pere, Juliette Eugène Lamer, Stéphane Bézieau, Tamara Matysiak, Roger Faroux, François-Xavier Caroli Bosc, Marie-Christine Rousselet, François Leclair, Jean-François Mosnier, Claire Toquet, Nadine Gervois, and Céline Bossard

Subjects
cetuximab, metastatic colorectal carcinoma, CD16, tumor-associated neutrophils, antibody-dependent cellular cytotoxicity, HLA-E/NKG2A axis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Antibody-dependent cellular cytotoxicity (ADCC) in the anti-tumor effect of cetuximab in metastatic colorectal cancer (mCRC) is only based on the impact of FcγRIIIA (CD16) polymorphisms as predictive of therapeutic response. However, nature, density and therapeutic impact of FcγRIIIA+ (CD16) effector cells in tumor remain poorly documented. Moreover, the inhibition of cetuximab-mediated ADCC induced by NK cells by the engagement of the new inhibitory CD94-NKG2A immune checkpoint has only been demonstrated in vitro. This multicentric study aimed to determine, on paired primary and metastatic tissue samples from a cohort of mCRC patients treated with cetuximab: 1) the nature and density of FcγRIIIA+ (CD16) immune cells, 2) the expression profile of HLA-E/β2m by tumor cells as well as the density of CD94+ immune cells and 3) their impact on both objective response to cetuximab and survival. We demonstrated that FcγRIIIA+ (CD16) intraepithelial immune cells mainly correspond to tumor-associated neutrophils (TAN), and their high density in metastases was significantly associated with a better response to cetuximab, independently of the expression of the CD94/NKG2A inhibitory immune checkpoint. However, HLA-E/β2m, preferentially overexpressed in metastases compared with primary tumors and associated with CD94+ tumor infiltrating lymphocytes (TILs), was associated with a poor overall survival. Altogether, these results strongly support the use of bispecific antibodies directed against both EGFR and FcγRIIIA (CD16) in mCRC patients, to boost cetuximab-mediated ADCC in RAS wild-type mCRC patients. The preferential overexpression of HLA-E/β2m in metastases, associated with CD94+ TILs and responsible for a poor prognosis, provides convincing arguments to inhibit this new immune checkpoint with monalizumab, a humanized anti-NKG2A antibody, in combination with anti- FcγRIIIA/EGFR bispecific antibodies as a promising therapeutic perspective in RAS wild-type mCRC patients.

Published
2021
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4. Comparison of 4 Screening Methods for Detecting Fluoropyrimidine Toxicity Risk: Identification of the Most Effective, Cost-Efficient Method to Save Lives

Author

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

Subjects
Therapeutics. Pharmacology, RM1-950
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 (UH 2 /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, UH 2 /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
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5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. Carcinoembryonic Antigen Levels and Survival in Stage III Colon Cancer

Author

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

Subjects
Male, Colonic Neoplasms, Humans, Female, Survival Analysis, Carcinoembryonic Antigen, Neoplasm Staging
Abstract

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.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.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 level5 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 (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.CEA levels should be applied more accurately in future trials and clinical practice.

Published
2018

23. 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

24. 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

25. 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

26. 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

27. Evaluation in usual practice of the bevacizumab-FOLFIRI combination for the first-line treatment of patients with unresectable metastatic colorectal cancer treated in 2006: focus on resected patients and oncogeriatrics

Author

C. Riche, J. F. Bouret, N. A. Achour, M. I. Labarre, L. Derenne, A. Ulvoas, D. Martin, Hugues Bourgeois, P. Leynia, T. Matysiak Budnik, G. Piriou, P. L. Etienne, A. M. Vidal, V. Rossi, P. Michel Langlet, D. Déniel Lagadec, Marc Porneuf, M. N. Julien, Olivier Capitain, C. Chouzenoux, E. Jobard, C. Naveau Ploux, Isabelle Cumin, Olivier Dupuis, Loïc Campion, Claire Stampfli, Jean-Yves Douillard, Erick Gamelin, C. Bertrand, A. Brouard, L. Guivarch, V. Guérin Meyer, E. Peguet, Fanny Marhuenda, E. Boucher, Jean-Philippe Metges, L. Miglianico, S. Roussel, A. S. Le Bris Michel, F. Royet, J. Faycal, A. Gourlaouen, P. Thomaré, D. Grasset, F. Riaud, C. Louvigné, Hélène Senellart, S. Barré, S. Rochard, M. Couturier, Oana Cojocarasu, S. Gouva, H. Desclos, J. Egreteau, C. Bertholom, C. Bodin, M. A. Lebot, Jean-Luc Raoul, G. Le Bihan, V. Bicheler, V. Klein, F. Grude, C. Elhannani, R. Largeau, Philippe Deguiral, Roger Faroux, F. Suberville, B. Person, R. Bessard, C. Grollier, E. Crespeau, and Jean-François Ramée

Subjects
Oncology
Abstract

En 2006, bevacizumab-FOLFIRI represente la therapie ciblee administrable des la premiere ligne chez les patients porteurs d’un cancer colorectal metastatique non operable. Une serie homogene de 111 patients colliges en region Bretagne et Pays de la Loire ayant recu du bevacizumab- FOLFIRI en premiere ligne en 2006 revele les resultats suivants: 51 reponses, 29 stabilites, 21 progressions et 10 toxicites avant evaluation. La mediane de survie globale (OS) est de 25,1 mois et la mediane de survie sans progression (PFS) de 10,2 mois. Dans le cas d’une chirurgie secondaire, l’OS median triple de 18,8 mois chez les patients non reseques versus 59,2 mois ceux reseques. En comparant les sujets âges de plus et de moins de 70 ans, aucune difference n’a ete mise en evidence en termes de benefice ou de risque. Bevacizumab-FOLFIRI pourrait etre administre en pratique courante chez les personnes âgees sous couvert d’une evaluation geriatrique et d’une approche multidisciplinaire.

Published
2014

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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

36. Multifactorial pharmacogenetic analysis in colorectal cancer patients receiving 5-fluorouracil-based therapy together with cetuximab-irinotecan

Author

Chaza El Hannani, Isabelle Hennebelle, Roger Faroux, Mireille Francoual, Eric Francois, J.H. Jacob, Gérard Milano, Marie-Christine Etienne-Grimaldi, Jean-Louis Formento, Jaafar Bennouna, Jean-Yves Douillard, and Etienne Chatelut

Subjects
Pharmacology, Oncology, medicine.medical_specialty, biology, Cetuximab, Colorectal cancer, FCGR3A, FCGR2A, medicine.disease, Folinic acid, Methylenetetrahydrofolate reductase, Internal medicine, Genotype, biology.protein, medicine, Pharmacology (medical), Pharmacogenetics, medicine.drug
Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Previous pharmacogenetic studies have reported the potential predictive value of thymidylate synthase (TYMS) polymorphisms or methylenetetrahydrofolate reductase (MTHFR) polymorphisms for the efficacy of 5-fluorouracil-based therapy, even though they have not yet been fully validated. Also, functional polymorphisms of genes linked to the epidermal growth factor receptor pathway [epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR)], as well as polymorphisms of genes encoding for Fcγ receptors [Fc fragment of IgG receptor 2A (FCGR2A) and 3A (FCGR3A)], which influence their affinity for the Fc fragment, have been reported to be linked to the pharmacodynamics of cetuximab in the clinical setting. WHAT THIS STUDY ADDS • This prospective study conducted on advanced colorectal cancer patients receiving first-line tegafur-uracil–irinotecan–cetuximab therapy suggests that a favourable genotype score, considering both the TYMS 3RG allele and any Val-containing FCGR3 allele, may be an indicator of better clinical response and longer overall survival. AIM To examine the predictive value of gene polymorphisms potentially linked to toxicity, clinical response, time to progression and overall survival, following cetuximab–tegafur-uracil (UFT)–irinotecan therapy. METHODS Fifty-two patients with advanced colorectal cancer were enrolled in an ancillary pharmacogenetic study of the phase II CETUFTIRI trial. Treatment consisted of 21 day cycles of cetuximab (day 1–day 8–day 15, 250 mg m−2 week−1 following a 400 mg m−2 initial dose) together with irinotecan (day 1, 250 mg m−2) and UFT–folinic acid (days 1–14, 250 mg m−2 day−1 UFT, 90 mg day−1 folinic acid). Analysed gene polymorphisms (blood DNA) were as follows: EGFR (CA repeats in intron 1, −216G>T, −191C>A), EGF (61A>G), FCGR2A (131Arg>His), FCGR3A (158Phe>Val), UDP-glycosyltransferase1-polypeptide A1 (TA repeats), TYMS (28 bp repeats, including the G>C mutation on the 3R allele, 6 bp deletion in 3′ UTR) and MTHFR (677C>T, 1298A>C). RESULTS Maximum toxicity grade was linked to EGFR−191C>A polymorphism, with 71.1% grade 3–4 toxicity in CC patients vs. 28.6% in other patients (P= 0.010). A tendency to a better response was observed in patients bearing the TYMS 3RG allele (P= 0.029) and those bearing the FCGR3A 158Val genotype (P= 0.020). The greater the score of favourable TYMS and FCGR3A genotypes, the better the response rate (P= 0.009) and the longer the overall survival (P= 0.007). In multivariate analysis, the score of favourable genotypes was a stronger survival predictor than the performance status. CONCLUSIONS Present data suggest the importance of FCGR3A 158Phe>Val and TYMS 5′ UTR polymorphisms in responsiveness and survival of patients receiving cetuximab–fluoropyrimidine-based therapy.

Published
2012

37. High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn’s Disease

Author

Laurent Beaugerie, Fabrice Carrat, Stéphane Nahon, Jean-David Zeitoun, Jean-Marc Sabaté, Laurent Peyrin-Biroulet, Jean-Frédéric Colombel, Matthieu Allez, Jean-François Fléjou, Julien Kirchgesner, Magali Svrcek, Jacques Cosnes, Jean-Pierre Gendre, Marc Lémann, Xavier Hébuterne, Antoine Cortot, Yoram Bouhnik, David Laharie, Jean Louis Dupas, Bernard Flourié, Eric Lerebours, Bernard Messing, Guillaume Cadiot, Philippe Marteau, Jean-Claude Soulé, Jean-Marc Gornet, Michel Veyrac, Bernard Duclos, Philippe Beau, Arnaud Bourreille, Philippe Baumer, Franck Carbonnel, Denis Heresbach, Etienne-Henry Metman, Christian Florent, Antoine Blain, Jean-Luc Faucheron, Bruno Bonaz, Xavier Roblin, Pascal Potier, Christian Boehm, Thierry Kurtz, Hervé Lamouliatte, Isabelle Nion-Larmurier, Jean-Charles Delchier, Stanislas Chaussade, Anne Marie Weiss, Jean Pierre Cézard, Laurent Siproudhis, Daniel Sondag, Raymond Jian, Jean-Christophe Souquet, Pierre Bord, Benoit Coffin, Hélène D’almagne, Patrick Delasalle, Régis Fournier, Maryan Cavicchi, Marc-Henry Souffran, Luc Vandromme, Claire Guedon, Philippe Seksik, Christophe Michiels, Pascal Renard, Patrice Rogier, Sylvie Gouilloud, André Rotenberg, Guillaume Savoye, Alain Thevenin, Laurent Mallet, Franck Brazier, Francois Jean, Anne-Marie Justum, Jean-Paul Latrive, Jean-Luc Gerbal, Robert Pierrugues, Gérard Chardonnal, Laurence Picon, Nicole Reix, Nicolas Drouët D’aubigny, Hervé Uettwiller, Anne Courillon Mallet, Alain Palacci, Raoul-Jacques Bensaude, Pierre Bonniaud, Olivier Empinet, Andrée Nisard, Alain Rudelli, Bernard Tubiana, Philippe Capelle, Alain Dabadie, Daniel Evard, Pierre-Emile Julien, Magali Picon-Coste, Stéphane Schneider, Denis Goldfain, Jérôme Bellanger, Jean-Pierre Blondelot, Philippe Lamy, Sébastien Lemière, Jean Francois Mockly, Benoit Pellat, Gilles Gatineau-Sailliant, Bernard Nalet, Stéphane Nancey, Daniel Kusielewicz, Patrick Loison, Jean-Michel Popot, François Merite, Jean-Pol Roux, Pauline Afchain, Alain Blanquart, Laurent Heyries, Marc Reville, Dominique Viron, Frank Zerbib, Christophe Claviere, Didier Léostic, Philippe Pouderoux, Alain Moitry, Hervé Hagège, Jean-Pierre Hugot, Benoit Humeau, Jean-Marc Sabate, Emmanuel Lederman, Dominique Lescut, Fabrice Luneau, Bruno Mesnard, Lionel Smadja, Michel Steinberg, Marc Brun, Gilles Macaigne, Jean Luc Marchal, Stéphane Ollivier, Dominique Ouvry, Jean Paul Perche, Serge Rambaud, Robert Benamouzig, Jean Louis Cazenave, Jean-Charles Coffin, Martine Blazquez, Marion Lagneau, Bruno Person, Christian Wittersheim, Bertrand Napoleon, Israël Cemachovic, Franck Iglicki, Mehran Howaizi, Eric Leprince, Bruno Leurent, Thierry Morin, Riad Darsouni, Alain Attar, Philippe Baron, Anne Breton, Jean Marie Gillion, Jean-Marc Guemene, Claude Jouffre, Xavier Moreau, Pierre Claude, André Quinton, Vered Abitbol, Jean Michel Brichard, Benoit Desaint, Martin Bouygues, Philippe Chatrenet, Marcelo Salmeron, Jean Silvie, Bruno Waldner, Yves Emery, Armand Moraillon, Daniel Kunkel, Philippe Dubois, Patrick Faure, Christian L'Hirondel, Jean-Eric Labérenne, Pierre Moreau, Adelino Pereira, Genevieve Plihon, Thierry Wolff, Yann Ngo, Arnaud Boruchowicz, Béatrice Jost, Jean Pierre Gotlib, Odile Danne, Philippe Raoux, Marie-José Ramond-Bouhali, Andre Baetz, Bruno Veyres, Christian Chapoutot, Gérard Le Dréau, Jérôme Filippi, Jean Mudry, Philippe Kalt, Sophie Minault, Pierre-André Bounin, Tony Andréani, Jacky Charneau, Didier Reijasse, Jean-Louis Bolze, Jean Luc Thaunat, Christian Le Couteulx, Chantal Maurage, Robert Bader, Philippe Codjovi, Jean-Luc Migairou, Alain Morali, Philippe Rey, Bruno Richard Molard, Richard Petit, Stéphane Koch, Philippe Cassan, Jean-Paul Deschamps, Christine Meicler Caby, Jean-Jacques Meurisse, Philippe Prades, James Boulant, Michel Diacono, Jean-Marie Monsch, J-François Dupuy, Guy Bellaiche, Martine Guegan, Jean-Marc Comte, Jean-Michel Cayla, Francois Le Tallec, Franck Meurisse, Philippe Desurmont, Laurent Roget, Philippe Bouyssou, Bruno Le Gall, Francis Bloch, Loic Larvol, Monique Jullien, Jacques Moreau, Laurent Rebouissoux, Bruno Decroix, Nina Dib, Paul Dieterling, Frédéric Lenormand, Emmanuel Lagier, Philippe Fallourd, Serge Charpin, Hugues Bertrand, Gilles Bommelaer, Daniel Battistelli, Bernard Delon, Lionel Dentant, Etienne Dorval, Jérôme Dumortier, Eric Gaye-Bareyt, Yves Gerosa, Chantal Guez, Martine Mornet, Paul Benfredj, René Piperaud, Noel Stremsdoerfer, Eric Verdier, Alain Grinholtz, Georges Barjonet, Antoine See, Ramuntxo Arotçarena, Anne Baudet, Joel Broyer, Antoine Charachon, Hugues Blondon, Pascal Mouton, Hubert Claudez, Jacques Labat-Labourdette, Jacques Haëm, Patrick Estable, Patrick Levy, Alain Rosenbaum, Yvon Balavoine, Alain Blanchi, Pierre Coutarel, Nadege Delaperriere, Michel Dervichian, Francis Marois, Jacques Seroka, Laurent Michaud, Olivier Leroy, Emmanuel Meyran, Bernard Poilroux, Abdallah Tensaouti, Thierry Paupard, Dominique Agard, Sandrine Beaulieu, Kader Benfiguig, Patrice Capony, Jean Cottereau, Pierre Desreumaux, Jean-Michel Dramard, Mathieu Duché, Patrick Mamou, Isabelle Etienney, Gilles D'Abrigeon, Béatrice Godeberge, Gilbert Tucat, Jean Puech, Jean Roger, Marie-George Lapalus, Paul Bauret, Philippe Houcke, Béatrice Pornin, Bruno Champigneulle, Laurent Cuissard, Xavier-Richard David, Frédéric Lombard, Antoine Granveau, Jean-François Hamon, Olivier Ink, Fabienne Blondel, Alain Namias, Didier Pillon, Antoine Reignier, Gilles Tordjman, Christos Christidis, Simon Zirabe, Michel Audebert, Eric Bion, Claude Bourgeaux, Cécile Poupardin, Philippe Deplaix, Gérard Fratini, Thierry Garnier, Gerard Desseaux, Hervé Magois, Sylvain Lochum, Jean-Francois Vergier, Patrick Texereau, Christel Rat, Francoise Uzzan, Alain Vidal, Nadia Vinante, Bernard Watrin, Cécile Wurtz-Huckert, Bruno Barre, Dominique Chaslin Ferbus, Jean-François Contou, Dominique Coupier, Benoit David, Dany Gargot, Denis Huc, Remy Barraya, Roger Faroux, Jean-Luc Fourgeaud, Hubert Grimprel, Jean Auroux, Jean-François Rey, Jean Pierre Arnoux, Franck Lentini, Ludovic Tardy, Olivier Mouterde, Claire Spyckerelle, Bruno Vacherot, Alain Weissman, Michel Alpérine, Anne Le Sidaner, Pierre-Olivier Bonnet-Eymard, Jean Louis Colson, Daniel Pellet, Bernard Deltombe, André Edouard, Henri Maechel, Jean-Claude Jaillet, Julien Genes, Anne-Marie Leveque, Damien Lucidarme, Philippe Maignan, Nathalie Mallier Gehrke, Jérôme Sanchez, Frank Tusseau, Alban Casteur, Jacques Bottlaender, Denis Constantini, Thierry Coton, Philippe Even, Francois Druart, François Riot, Jean-Michel Gauchet, Geneviève Hecquet, Gerard Henry, Patrick Hochain, Jean Pierre Arpurt, Abdelkrim Medini, Michele Dartois-Hoguin, Henri Moindrot, Philippe Emery, Pierre Periac, Annie Prunier, Pascal Renkes, Christine Tawil-Longreen, Edmond Vincent, René-Louis Vitte, Christian Loeb, Alain Carwana, Didier Barbereau, Philippe Bohon, Céline Corrieri-Baizeau, Daniel Sahy, Philippe Derreveaux, Dominique David, François Desbazeille, Patrick Fontenelle, Jean Luc Slama, Yvon Le Mercier, Michel Certin, Jean Jacques Reig, Isabelle Rosa, Thierry Helbert, Patrick Tounian, Luc Turner, Valéry Perot, Luc Aillet, Arnaud Pauwels, Philippe Barré, Bernard Nury, Claude Cazalbou, Franck Devulder, Alain Durget, Jeanne Dubroca, Daniele Gaudy, Michel Greff, Christian Jacques, Jocelyne Lafarge, Gilles Kezachian, Ronan Le Gall, Alex Pariente, Tiphaine Pinault, Michaël Bismuth, Nathalie Boyer-Darrigrand, Philippe Bretagnolle, Stephane Carpentier, Franck Cholet, Christian Theodore, Rémi Combes, Francois Combet, Christophe Delanoe, Stéphanie De Montigny, Denis Soudan, Olivier Fourdan, Gilles Minier, Jeanne Languepin, Jean Roche, Jean-Louis Ginies, Olivier Nouel, Philippe Petitgars, Edith Robin, Romain Hamm, Jean François Roques, Sylvie Roussin-Bretagne, Agnès Sénéjoux, Sophie Muron, Nicolas Bardoux, Philippe Berthelemy, Patrick Madonia, Bertrand Carles, Catherine Reynier, Emmanuel Cuillerier, Innocenti Dadamessi, Jacques Danis, Bernard Debenes, Nathalie Dubuc-Rey, Gilles Lesur, Pauline Jouet, Catherine Lenaerts, Marc Garret, Alexandra Mineur, Bernard Chabry, Francois Pigot, Valérie Rossi, Ruth Tennenbaum, Julien Salloum, Maurice Hakim Slaoui, Stéphane Mathieu, Valérie Papapietro, Sheila Viola, Alexis Bezet, Claude Altman, Alain Audan, Jean Calabet, Claude Masliah, Laurent Fayemendy, Marc Duruy, Benoit Gauffeny, Ludovic Helie, Kamran Imani, Raoul Janin-Manificat, Jean-Paul Galmiche, Anne Kerlirzin, Laurent Bedenne, Christophe Locher, Gilles Michaudel, Gilles Missonnier, Michel Rinaldi-Dovio, Jean-Michel Rouillon, Stéphane Ecuer, Arnaud Patenotte, Jean Ariel Bronstein, Vincent Baty, Michel Bougnol, Pierre Bourbon, Philippe Cerbelaud, Annick Chavaillon, Franck Boiffin, Béatrice Dubern, Isabelle Duval De Laguierce, Fernand Greco, Florence Bouhot, Philippe Godeberge, Brigitte Grandmaison, Pascal Gros, Guy Targues, Jacques Corallo, Jean Boutin, Jacques Guillan, Jean Pierre Barbieux, Isabelle Loury Lariviere, Henri Le Genissel, Henri Leroi, Marc Bellaiche, Marie-Claire Elie-Legrand, Michel Dapoigny, Philippe Denoyel, Patrice Pienkowski, Philippe Pouche, Marc Michel Saurfelt, Jean Marie Thorel, Thierry Piche, Bruno Travers, Patrick Tuvignon, Marc Zalcberg, Guy Boulay, Christophe Zamora, Joelle Samama, Etienne Ricotie, Patrice De Fleury, Francois Maille, Jean Louis Mougenel, Olivier Gonot, Jean Philippe Menat, Mehdi Kaassis, Francoise Lang, Laurent Abramowitz, Nathalie Ganne, Olivier Pecriaux, Jacques-Arnaud Seyrig, Iradj Sobhani, Thierry Parmentier, Antoine Van Nieuwenhuyse, Francois-Xavier Weber, André Glibert, Catherine Bineau, Bernard Canet, Catherine Collin, Frederic Cordet, David David Parlier, Dominique Carre, Annie Peytier, Francine Fein, Jerome Barouk, Jacques Dewannieux, Johannes Hartwig, Jean-Louis Jouve, Bertrand Laplane, Gilles Lascar, Christophe Legrand, Pierre Le Marchand, Marie Pierre Liebaert, Michele Terdiman-Pire, Naceur Abdelli, Dominique Neveu, Philippe De La Lande, Patrick De Saint Louvent, Cécile Pelatan, Agnès Petit, Martial Richecoeur, Frederic Texier, Jean Brice Cazals, Bertrand Tissot, Christian Mourrut, Marie Doubremelle, Marc Foltz, Florence Gautier-Jubé, Jacques Martin, Elie Khouri, Thierry Lons, Martine Carlier-Bandu, Jean-Luc Monnin, Hervé Roche, Bernard Willemin, Xavier Houard, Abdelaziz Fatisse, Michèle Algard, Kamel Arab, Isabelle Borel, Cécile Lagarrigue, Ariane Chryssostalis, Dominique Boutroux, Jean-Pierre Dupuychaffray, Saïd Khaddari, François Mion, Thierry Puy-Montbrun, Jean-Philippe Girardet, Bruno Gury, Alain Landau, Monique Le Bihan, Sandrine Nieuviarts, Jean Ollivry, Philippe Le Bourgeois, Marie-Astrid Piquet, Michel -Pierre Escartin, Remi Systchenko, Franck Venezia, Michel Wantiez, Xavier Lesage, Elie Zrihen, Philippe Aygalenq, Barbara Dieumegard, Bernard Savarieau, Philippe Bulois, Stéphane Cattan, Jean-Lucien Diez, Olivier Fauchot, Eric Durous, Valérie Gazut, Christian Guilleminet, Jean-Marc Bories, Isabelle Joly Le Floch, Jean-Paul Vove, Stéphane Lelouch, Philippe Lévy, François Lhopital, Norma Marcato, Marianne Mozer-Bernardeau, Jean-Baptiste Nousbaum, Philippe Cattan, Alain Plane, Jean-Michel Raymond, Gilles Roseau, Gerald Rozental, Christian Boustière, Corinne Bonny, Mariepierre Cordier-Collet, Laurent Courat, Bernard Croguennec, Karine Delaunay- Tardy, Damien Labarriere, Edmond Geagea, Frédéric Gottrand, Eve Gelsi, Gerard Thiefin, Eric Wohlschies, Mathieu Miguet, Philippe Ponsot, Jean Suzanne, Yves Teste, Anne-Claire Dupont Gossart, Jean-Luc Baroni, Benabdallah Benchaa, Georges Blanc, Bernard Maroy, Philippe Bonjean, Catherine Brézault, Laure Bridoux-Henno, Claude Chayette, Dominique Auby, Robert Fiorucci, Georges Galindo, Gilles Hubert, Gilles Bonneau, Evelyne Marinier, Michele Pouteau, Afchine Alamdari, Bruno Delbende, Patrick Chamouard, Pascale D'Abravanel, Hélène Dall'Osto, Sophie Hervé, Jean Lefebvre, Damien Levoir, Philippe Lillo, Michel Rouch, Muriel Mathonnet, Mercédes De Lustrac, François-Jean Ramond, Bernard Roupret, and Alain Soupison

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Colorectal cancer, Population, Risk Assessment, Gastroenterology, Inflammatory bowel disease, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Risk Factors, Internal medicine, medicine, Humans, Anal cancer, education, Aged, education.field_of_study, Crohn's disease, Hepatology, Rectal Neoplasms, business.industry, Incidence, Cancer, Odds ratio, Middle Aged, Anus Neoplasms, medicine.disease, Ulcerative colitis, Case-Control Studies, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, France, business, Follow-Up Studies
Abstract

Background & Aims Little is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn's disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn's perianal disease followed up in the Cancers Et Surrisque Associe aux Maladies Inflammatoires Intestinales En France (CESAME) cohort. Methods We collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn's disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex. Results Among the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn's lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn's disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03). Conclusions In an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn's disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer.

Published
2018

38. Quality-of-life findings from a randomised phase-III study of XELOX vs FOLFOX-6 in metastatic colorectal cancer

Author

Gérard Lledo, Jaafar Bennouna, J.-Y. Douillard, Mohamed Hebbar, Thierry Conroy, Christine Rebischung, Michel Ducreux, Roger Faroux, Leila Kockler, Antoine Adenis, and M. Ychou

Subjects
Male, QoL, Cancer Research, medicine.medical_specialty, Randomization, Organoplatinum Compounds, Oxaloacetates, Leucovorin, colorectal cancer, Adenocarcinoma, Deoxycytidine, law.invention, Capecitabine, Patient satisfaction, Randomized controlled trial, FOLFOX, Quality of life, law, Surveys and Questionnaires, Internal medicine, Clinical Studies, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Prospective Studies, Prospective cohort study, Aged, business.industry, capecitabine, QLQ-C30, Middle Aged, digestive system diseases, humanities, Oxaliplatin, Surgery, Oncology, Patient Satisfaction, CCSQ-FACIT, Quality of Life, Female, Fluorouracil, Colorectal Neoplasms, business, medicine.drug
Abstract

Background: A phase-III trial showed the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) in terms of efficacy in first-line treatment of metastatic colorectal cancer. A secondary objective was to compare the quality of life (QoL) and health-care satisfaction of patients. Methods: Patients were randomised to receive XELOX (n=156) or FOLFOX-6 (n=150) for 6 months. Quality of life and satisfaction were assessed by the Quality of Life Questionnaire-C30 (QLQ-C30) and Functional Assessment of Chronic Illness Therapy Chemotherapy Convenience and Satisfaction Questionnaire (FACIT-CCSQ), respectively. Patients completed questionnaires at baseline, at Cycle3 (C3) and Cycle (C6) (XELOX) or at C4 and C8 visits (FOLFOX-6) and at their final visit. Results: A total of 245 and 225 patients were assessed using QLQ-C30 and FACIT-CCSQ, respectively. The completion rates were >80%. Global QoL scores did not differ significantly between groups during the study. According to FACIT-CCSQ, XELOX seemed more convenient (C3/C4, P

Published
2009

39. Combinations of Cytochrome P450 Gene Polymorphisms Enhancing the Risk for Sporadic Colorectal Cancer Related to Red Meat Consumption

Author

Sébastien Küry, Louis-Dominique Chupin, Roger Faroux, Stéphane Bézieau, Bernard Lafraise, Sébastien Robiou-du-Pont, Jérémie Bourdon, Bruno Buecher, Tanguy Le Neel, Claire Le Houérou, Jean Ollivry, Véronique Sébille, Catherine Scoul, Hélène Colman, Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Université de Nantes (UN), Laboratoire d'Informatique de Nantes Atlantique (LINA), Centre National de la Recherche Scientifique (CNRS)-Mines Nantes (Mines Nantes)-Université de Nantes (UN), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), and Genetic Lab

Subjects
Male, Pathology, Epidemiology, MESH: Aryl Hydrocarbon Hydroxylases, Cohort Studies, MESH: Genotype, MESH: Aged, 80 and over, 0302 clinical medicine, Cytochrome P-450 Enzyme System, Risk Factors, MESH: Risk Factors, Genotype, Medicine, MESH: Cohort Studies, Aged, 80 and over, MESH: Aged, MESH: Meat, Genetics, 0303 health sciences, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, Cytochrome P-450 CYP2E1, Middle Aged, MESH: Case-Control Studies, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, MESH: Cytochrome P-450 CYP1A2, Oncology, Red Meat Consumption, 030220 oncology & carcinogenesis, Cytochrome P-450 CYP1B1, MESH: Cytochrome P-450 Enzyme System, Red meat, Female, Aryl Hydrocarbon Hydroxylases, France, Colorectal Neoplasms, Adult, medicine.medical_specialty, Meat, CYP1B1, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, 03 medical and health sciences, MESH: Diet, Cytochrome P-450 CYP1A2, Humans, Genetic Predisposition to Disease, Genetic variability, Allele, Alleles, Aged, Cytochrome P-450 CYP2C9, 030304 developmental biology, MESH: Humans, business.industry, MESH: Alleles, Case-control study, MESH: Adult, MESH: Male, Diet, MESH: France, MESH: Cytochrome P-450 CYP2E1, Case-Control Studies, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, MESH: Female, MESH: Colorectal Neoplasms
Abstract

Susceptibility to sporadic colorectal cancers (CRC) is generally thought to be the sum of complex interactions between environmental and genetic factors, all of which contribute independently, producing only a modest effect on the whole phenomenon. However, to date, most research has concealed the notion of interaction and merely focused on dissociate analyses of risk factors to highlight associations with CRC. By contrast, we have chosen a combinative approach here to explore the joint effects of several factors at a time. Through an association study based on 1,023 cases and 1,121 controls, we examined the influence on CRC risk of environmental factors coanalyzed with combinations of six single nucleotide polymorphisms located in cytochrome P450 genes (c.−163A>C and c.1548T>C in CYP1A2, g.−1293G>C and g.−1053C>T in CYP2E1, c.1294C>G in CYP1B1, and c.430C>T in CYP2C9). Whereas separate analyses of the SNPs showed no effect on CRC risk, three allelic variant combinations were found to be associated with a significant increase in CRC risk in interaction with an excessive red meat consumption, thereby exacerbating the intrinsic procarcinogenic effect of this dietary factor. One of these three predisposing combinations was also shown to interact positively with obesity. Provided that they are validated, our results suggest the need to develop robust combinative methods to improve genetic investigations into the susceptibility to CRC. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1460–7)

Published
2007

40. Postoperative irinotecan in resected stage II-III rectal cancer: final analysis of the French R98 Intergroup trial

Author

Ayman Zawadi, T. Andre, Marc Buyse, E. Quinaux, Olivier Dupuis, Pascal Piedbois, Veronique Guerin-Meyer, Philippe Rougier, Marc Ychou, Catherine Delbaldo, A. Jouhaud, J.-Y. Douillard, Roger Faroux, Groupe Hospitalier Diaconesses Croix Saint-Simon, 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), Institut du Cancer de Montpellier (ICM), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CRLCC René Gauducheau, Cooperator Multidisciplinary Oncology Group (GERCOR), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, 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 Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], CHU Henri Mondor, International Drug Development Institute (IDDI), and CRLCC Paul Strauss

Subjects
Male, Time Factors, Colorectal cancer, Leucovorin, 0302 clinical medicine, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, 5-fluorouracil, 030212 general & internal medicine, irinotecan, Aged, 80 and over, Hazard ratio, Hematology, Middle Aged, 3. Good health, adjuvant chemotherapy, Treatment Outcome, Oncology, Chemotherapy, Adjuvant, Fluorouracil, 030220 oncology & carcinogenesis, Early Termination of Clinical Trials, Disease Progression, Female, France, medicine.drug, Adult, safety, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, Disease-Free Survival, 03 medical and health sciences, Statistical significance, medicine, Humans, rectal cancer, Aged, Neoplasm Staging, Rectal Neoplasms, business.industry, medicine.disease, Survival Analysis, phase III, Surgery, Irinotecan, Regimen, Camptothecin, business
Abstract

Backgroud The R98 trial explores the addition of irinotecan to a 5-fluorouracil (5-FU) plus leucovorin (5-FU/LV) adjuvant regimen in optimally resected stages II–III rectal cancers. We report the updated long-term results. Disease-free survival (DFS) was the primary end point. Patienst and methods Between March 1999 and December 2005, 357 patients were randomized: 178 in 5-FU/LV and 179 in LV5-FU2 + irinotecan arm. The trial was stratified by control arm: Mayo Clinic regimen or LV5-FU2 regimen. Results Three hundred and fifty-seven randomized patients were evaluable for efficacy. With a follow-up of 156 months, the DFS was in favour of experimental arm but did not reach statistical significance [hazard ratio (HR) = 0.80, P = 0.154]. The same was observed for overall survival (OS) (HR = 0.87, P = 0.433). The 5-year DFS was 58% in the control arm and 63% in the experimental arm. The 5-year OS was 74% in the control arm and 75% in the experimental arm. Patients allocated to the experimental arm had more grade 3–4 neutropenia when compared with the LV5-FU2 arm (33% versus 6%, P = 0.03), but not when compared with the Mayo Clinic arm (33% versus 36%, P = 0.84). Grade 3–4 diarrhoea tended to be higher in the experimental arm, but analyses stratified by control arm or by radiotherapy failed to show significant differences across strata (test for interaction P = 0.44). Conclusion Even though a benefit of irinotecan in subgroups of patients cannot be excluded, due to early termination and lack of power, the study does not support the addition of irinotecan to 5-FU/LV in routine in patients with resected stage II–III rectal cancer.

Published
2015

41. O-0019 Severe Fluoropyrimidines Toxicities: A Simple and Effective Way to Avoid Them. Screen Effectively for DPD Deficiencies

Author

Alain Morel, Boisdron Michele-Celle, Jean-Philippe Metges, Veronique Guerin-Meyer, Chantal Leguellec, Roger Faroux, Erick Gamelin, Tamara Matysiak-Budnik, Claire Stampfli, and Olivier Capitain

Subjects
Oncology, medicine.medical_specialty, education.field_of_study, Chemotherapy, business.industry, medicine.medical_treatment, Population, Hematology, Capecitabine, FOLFOX, Internal medicine, Toxicity, medicine, FOLFIRI, DPYD, Mutation frequency, education, business, medicine.drug
Abstract

Introduction Severe, even fatal toxicities which occur during the first course of fluoropyrimidines chemotherapy treatments pose a serious public health problem. This family of chemotherapy molecules is used in over 60% of protocols, in adjuvant and metastatic settings. In adjuvant therapies, using fluoropyrimidines engenders a toxic (even fatal) risk to a patient who is possibly in remission, if not cancer-free. Even protocols using orally-administered molecules (capecitabine, UFT, others) cause the same toxicities. The results of more than 11,000 patients, assessing risk in the prevalence of severe toxicities by the search for mutations in the DPD and phenotyping are included in this study. Methods From April 2001 to December 2011, 11,351 patients were screened for the risk of severe toxic reaction to fluoropyrimidines. Chemotherapy protocols were 5-Fluorouracil based (e.g., FEC, LV5FU2, FOLFOX, FOLFIRI), as well as orally- delivered fluoropyrimidines (capecitabine and UFT.) 11,104 patients were screened before treatment, as has been the regular protocol in our institution. 247 blood samples were received from other institutions from patients who, after having received their first treatment, showed signs of severe (grade III-IV) toxicity, or had died. The evaluation of risk associates genotyping for mutations on the DPYD gene (1) and phenotyping (dihydrouracil and plasmatic uracil) (2). The calculations were made via the ODPM Tox (ODPM, Angers, France), and every patient whose screening before treatment showed risk received an individually-adapted dose via ODPM Protocol (ODPM, Angers, France). Results The frequencies of mutations observed in the total population are presented in Table I. The frequencies of mutations involved in serious toxicities with fluoropyrimidine are shown in Figure 1. In the patient population screened after toxicity occurred (247 patients): 27 patients (11%) died from toxicity. 16 patients (59%) had one or more genetic mutations and 11 presented with no mutation, but a phenotype characteristic of DPD deficit (ODPM Tox). 220 patients (89%) showed grade III – IV toxicity after first treatment (hematological, diarrhea, etc). Among these patients, 66 (30%) presented with genetic mutation and 148 (67%) showed altered phenotype (ODPM Tox). In population screened before treatment (11, 104): no patients died and none presented with grade III-IV toxicity. Among this population, 264 (2.4%) patients carried one or more risk-related mutations and 956 showed a phenotype characteristic of DPD deficiency. All of these patients received chemotherapy treatments using the ODPM Tox dose-adjustment and all subsequent rounds were dose-adjusted using ODPM Protocol. Conclusion The dual approach to DPD deficiency screening using genotype and phenotype (ODPM Tox) before treatment avoided all severe toxicities. This system has been used in our institution for the past 10 years on a routine basis. Only 8 patients (.07%), of which 2 presented with cardiac toxicity, neither carried a known mutation nor showed a phenotype for risk of toxicity. Thus, the technique has over 99.9% reliability. All of the patients who carried a known risk for toxicity were either treated by another protocol without fluoropyrimidines, or the 5-Fluorouracile treatments were dose-adjusted (ODPM Protocol). Download : Download full-size image Figure 1 . Frequencies of mutations involved in serious toxicities with fluoropyrimidne. Table I . Mutation frequency

Published
2012

42. Three versus six months’ adjuvant oxaliplatin-based chemotherapy for patients with stage III colon cancer: Per-protocol, subgroups and long-lasting neuropathy results

Author

Gael Deplanque, Dewi Vernerey, Jérôme Dauba, L. Mineur, C. Louvet, May Mabro, C. Lepere, Olivier Dupuis, Jaafar Bennouna, O. Bouche, T. Andre, Roger Faroux, S. Fratte, Jérôme Desramé, Yves Becouarn, F. Bonnetain, Marc Ychou, Julien Taieb, A. de Gramont, and Joëlle Egreteau

Subjects
0301 basic medicine, Oncology, Long lasting, medicine.medical_specialty, Chemotherapy, Intention-to-treat analysis, business.industry, medicine.medical_treatment, Hematology, Colon cancer stage iii, Oxaliplatin, Stage III Colon Cancer, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, Adjuvant, medicine.drug
Published
2017

43. A Phase 2b of eryaspase in combination with gemcitabine or FOLFOX as second-line therapy in patients with metastatic pancreatic adenocarcinoma (NCT02195180)

Author

T. Andre, C. Louvet, Julien Volet, David Tougeron, Christophe Tournigand, Jérôme Cros, L. Mineur, Fabienne Portales, Willy Berlier, Thierry Lecomte, Roger Faroux, C. de la Fouchardiere, J-B. Bachet, F. El Hajbi, J.-P. Metges, C. Rebischung, Iman El-Hariry, Rosine Guimbaud, Anu Gupta, and Pascal Hammel

Subjects
Oncology, medicine.medical_specialty, Second-line therapy, business.industry, Hematology, Metastatic Pancreatic Adenocarcinoma, Gemcitabine, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030211 gastroenterology & hepatology, In patient, business, medicine.drug
Published
2017

44. Adjuvant GEMOX for biliary tract cancer: Updated relapse-free survival and first overall survival results of the randomized PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial

Author

C. Louvet, E. Boucher, F. Bonnetain, M. Benabdelghani, J.F. Seitz, Laetitia Fartoux, Roger Faroux, Julien Edeline, Beata Juzyna, J-L. Jouve, Jérôme Watelet, Eric Assenat, David Malka, Aurélie Bertaut, Pascal Hammel, Karine Bouhier-Leporrier, J.M. Phelip, Trevor Stanbury, J-P. Joly, and Veronique Guerin-Meyer

Subjects
medicine.medical_specialty, Biliary tract cancer, business.industry, 05 social sciences, Hematology, GemOx, Relapse free survival, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Pharmaceutical Adjuvants, Oncology, 030220 oncology & carcinogenesis, Internal medicine, 0502 economics and business, medicine, Overall survival, 050211 marketing, business
Published
2017

45. PRODIGE 25 (FFCD 11-01) - Phase II randomized trial evaluating aflibercept associated with LV5FU2 regimen as first line treatment of non-resectable metastatic colorectal cancers (FOLFA)

Author

Jean-Louis Legoux, E. Maillard, Valérie Boige, Yann Touchefeu, Nicolas Barriere, M. Baconnier, Y. Rinaldi, Roger Faroux, Joëlle Egreteau, Thomas Aparicio, K. Le Malicot, S. Herrmann-Gandara, Cedric Lecaille, J. Raimbourg, and A. Vimal

Subjects
Oncology, medicine.medical_specialty, business.industry, Hematology, law.invention, First line treatment, Regimen, Randomized controlled trial, law, Internal medicine, Medicine, business, Aflibercept, medicine.drug
Published
2016

46. Multifactorial pharmacogenetic analysis in colorectal cancer patients receiving 5-fluorouracil-based therapy together with cetuximab-irinotecan

Author

Marie-Christine, Etienne-Grimaldi, Jaafar, Bennouna, Jean-Louis, Formento, Jean-Yves, Douillard, Mireille, Francoual, Isabelle, Hennebelle, Etienne, Chatelut, Eric, Francois, Roger, Faroux, Chaza, El Hannani, Jacques-Henri, Jacob, and Gérard, Milano

Subjects
Adult, Aged, 80 and over, Male, Epidermal Growth Factor, Antibodies, Monoclonal, Cetuximab, Thymidylate Synthase, Middle Aged, Antibodies, Monoclonal, Humanized, Irinotecan, Polymorphism, Single Nucleotide, ErbB Receptors, Pharmacogenetics, Antineoplastic Combined Chemotherapy Protocols, Humans, Camptothecin, Female, Fluorouracil, Prospective Studies, Colorectal Neoplasms, Methylenetetrahydrofolate Reductase (NADPH2), Aged
Abstract

To examine the predictive value of gene polymorphisms potentially linked to toxicity, clinical response, time to progression and overall survival, following cetuximab-tegafur-uracil (UFT)-irinotecan therapy.Fifty-two patients with advanced colorectal cancer were enrolled in an ancillary pharmacogenetic study of the phase II CETUFTIRI trial. Treatment consisted of 21 day cycles of cetuximab (day 1-day 8-day 15, 250 mg m(-2) week(-1) following a 400 mg m(-2) initial dose) together with irinotecan (day 1, 250 mg m(-2)) and UFT-folinic acid (days 1-14, 250 mg m(-2) day(-1) UFT, 90 mg day(-1) folinic acid). Analysed gene polymorphisms (blood DNA) were as follows: EGFR (CA repeats in intron 1, -216GT, -191CA), EGF (61AG), FCGR2A (131ArgHis), FCGR3A (158PheVal), UDP-glycosyltransferase1-polypeptide A1 (TA repeats), TYMS (28 bp repeats, including the GC mutation on the 3R allele, 6 bp deletion in 3' UTR) and MTHFR (677CT, 1298AC).Maximum toxicity grade was linked to EGFR-191CA polymorphism, with 71.1% grade 3-4 toxicity in CC patients vs. 28.6% in other patients (P= 0.010). A tendency to a better response was observed in patients bearing the TYMS 3RG allele (P= 0.029) and those bearing the FCGR3A 158Val genotype (P= 0.020). The greater the score of favourable TYMS and FCGR3A genotypes, the better the response rate (P= 0.009) and the longer the overall survival (P= 0.007). In multivariate analysis, the score of favourable genotypes was a stronger survival predictor than the performance status.Present data suggest the importance of FCGR3A 158PheVal and TYMS 5' UTR polymorphisms in responsiveness and survival of patients receiving cetuximab-fluoropyrimidine-based therapy.

Published
2012

47. Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer

Author

Michel, Ducreux, Jaafar, Bennouna, Mohamed, Hebbar, Marc, Ychou, Gérard, Lledo, Thierry, Conroy, Antoine, Adenis, Roger, Faroux, Christine, Rebischung, Loic, Bergougnoux, Leila, Kockler, Jean-Yves, Douillard, and J P, Wagner

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, Population, Leucovorin, Neutropenia, Gastroenterology, Deoxycytidine, Disease-Free Survival, Capecitabine, Young Adult, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, education, Aged, Neoplasm Staging, Aged, 80 and over, education.field_of_study, business.industry, Rectal Neoplasms, Middle Aged, medicine.disease, humanities, digestive system diseases, Surgery, Oxaliplatin, Regimen, Treatment Outcome, Oncology, Fluorouracil, Colonic Neoplasms, Female, business, Colorectal Neoplasms, Febrile neutropenia, medicine.drug
Abstract

A regimen consisting of 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) is widely used in France in the first-line treatment of metastatic colorectal cancer (MCRC). The aim of our study was to demonstrate the non-inferiority of capecitabine plus oxaliplatin (XELOX) versus FOLFOX-6 for this indication. Patients were randomly assigned to receive XELOX or FOLFOX-6 for 6 months. The primary endpoint was overall response rate (ORR) in the per-protocol (PP) population; however, progression-free and overall survival (OS), time to response and response duration were also assessed. A total of 306 patients were enrolled (XELOX n = 156; FOLFOX-6 n = 150). ORR was 42 and 46% with XELOX and FOLFOX-6, respectively, in the PP population. The difference between groups was 4.7%; the upper limit of the unilateral 95% confidence interval (14.4%) was below the non-inferiority margin of 15%. In the intent-to-treat population, median progression-free survival was 8.8 months with XELOX and 9.3 months with FOLFOX-6, and median OS was 19.9 and 20.5 months, respectively. XELOX patients had significantly more grade 3/4 thrombocytopenia (12% vs. 5%) and diarrhoea (14% vs. 7%), but significantly less grade 3/4 neutropenia (5% vs. 47%), febrile neutropenia (0% vs. 6%) and neuropathy (11% vs. 26%) than FOLFOX-6 patients. We conclude that XELOX is non-inferior in terms of efficacy to FOLFOX-6 in the first-line treatment of MCRC, but has a different toxicity profile.

Published
2010

49. Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study

Author

Bruno Buecher, Sébastien Küry, Jean Ollivry, Roger Faroux, Bernard Lafraise, Sébastien Robiou-du-Pont, Hélène Colman, Véronique Sébille, Catherine Scoul, Claire Le Houérou, Louis-Dominique Chupin, Tanguy Le Neel, and Stéphane Bézieau

Subjects
Adult, Male, Cancer Research, Genotype, Population, Single-nucleotide polymorphism, Penetrance, lcsh:RC254-282, Polymorphism, Single Nucleotide, Genetics, Medicine, Humans, Genetic Predisposition to Disease, Allele, education, Alleles, Genetic association, Aged, education.field_of_study, Models, Genetic, business.industry, Case-control study, Odds ratio, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, digestive system diseases, Logistic Models, Oncology, Case-Control Studies, Female, France, business, Colorectal Neoplasms, Research Article
Abstract

Background Sporadic colorectal cancers (CRC) are multifactorial diseases resulting from the combined effects of numerous genetic, environmental and behavioral risk factors. Genetic association studies have suggested low-penetrance alleles of extremely varied genes to be involved in susceptibility to CRC in Caucasian populations. Methods Through a large genetic association study based on 1023 patients with sporadic CRC and 1121 controls, we tested a panel of these low-penetrance alleles to find out whether they could determine "genotypic profiles" at risk for CRC among individuals of the French population. We examined 52 polymorphisms of 35 genes – drawn from inflammation, xenobiotic detoxification, one-carbon, insulin signaling, and DNA repair pathways – for their possible contribution to colorectal carcinogenesis. The risk of cancer associated with these polymorphisms was assessed by calculation of odds ratios (OR) using multivariate analyses and logistic regression. Results Whereas all these polymorphisms had previously been found to be associated with CRC risk, especially in Caucasian populations, we were able to replicate the association for only five of them. Three SNPs were shown to increase CRC risk: PTGS1 c.639C>A (p.Gly213Gly), IL8 c.-352T>A, and MTHFR c.1286A>C (p.Ala429Glu). On the contrary, two other SNPs, PLA2G2A c.435+230C>T and PPARG c.1431C>T (p.His477His), were associated with a decrease in CRC risk. Further analyses highlighted genotypic combinations having a greater predisposing effect on CRC (OR 1.97, 95%CI 1.31–2.97, p = 0.0009) than the allelic variants that were examined separately. Conclusion The identification of CRC-predisposing combinations, composed of alleles PTGS1 c.639A, PLA2G2A c.435+230C, PPARG c.1431C, IL8 c.-352A, and MTHFR c.1286C, highlights the importance of inflammatory processes in susceptibility to sporadic CRC, as well as a possible crosstalk between inflammation and one-carbon pathways.

Published
2008

50. Phase II study of UFT with leucovorin and irinotecan (TEGAFIRI): first-line therapy for metastatic colorectal cancer

Author

Françoise Desseigne, E. Francois, Jaafar Bennouna, Hervé Perrier, Pascal Artru, Denis Smith, Roger Faroux, F. Husseini, Roland Bugat, Jean Pierre Delord, Naman H, Pascal Piedbois, and J.-Y. Douillard

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Colorectal cancer, Leucovorin, Phases of clinical research, colorectal cancer, Neutropenia, Irinotecan, Tegafur, Gastroenterology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Clinical Studies, medicine, Humans, Neoplasm Metastasis, Uracil, UFT, Aged, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, Surgery, Regimen, Treatment Outcome, Oncology, Tolerability, Vomiting, Camptothecin, Female, medicine.symptom, business, Colorectal Neoplasms, first-line treatment, medicine.drug
Abstract

This phase II trial was performed to evaluate the efficacy and tolerability of oral tegafur-uracil (UFT) with leucovorin (LV) combined with intravenous (i.v.) irinotecan every 3 weeks (TEGAFIRI) as first-line treatment for patients with metastatic colorectal cancer (mCRC). Patients received oral UFT 250 mg m(-2) day(-1) and LV 90 mg day(-1) in three divided daily doses for 14 days followed by a 1-week rest and i.v. irinotecan 250 mg m(-2) as a 90-min infusion every 3 weeks. Tumour responses, assessed every two cycles using RECIST criteria, were reviewed by an independent review committee. In 52 evaluable patients, the best overall response rate was 33% (95% confidence intervals (CI) 20-47%; 1 complete and 16 partial responses). The median time to progression was 5.4 months (95% CI 3.02-7.52 months) and median overall survival was 14.9 months (11.73-17.97 months). A total of 307 cycles were administered, with a median number of five cycles per patient (range: 1-10). The most common grade 3/4 toxicities were neutropenia (25% of patients), diarrhoea (22%), vomiting (11%) and anaemia (11%). The TEGAFIRI regimen is a feasible, well-tolerated and convenient treatment option for patients with non-resectable mCRC.

Published
2007

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