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1. Discontinuation of first-line bevacizumab in metastatic colorectal cancer: the BEAWARE Italian Observational Study

Author

Lonardi, S., Nasti, G., Fagnani, D., Gemma, D., Ciuffreda, L., Granetto, C., Lucchesi, S., Ballestrero, A., Biglietto, M., Proserpio, I., Bergamo, F., Proietti, E., Tonini, G., and Soto Parra, H

Subjects
Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Genotype, Bevacizumab, Colorectal cancer, First line, Angiogenesis Inhibitors, Metastatic colorectal cancer, bevacizumab, clinical practice, progression-free survival, therapy interruption, Disease-Free Survival, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Progression-free survival, Neoplasm Metastasis, Aged, business.industry, General Medicine, Middle Aged, medicine.disease, Discontinuation, 030104 developmental biology, Italy, 030220 oncology & carcinogenesis, Mutation, Mutation (genetic algorithm), Female, Observational study, Colorectal Neoplasms, business, medicine.drug
Abstract

Aims: BEAWARE investigated the pattern of first-line bevacizumab early interruption in the Italian real-world setting of metastatic colorectal cancer. Methods: A total of 386 patients were followed for 15 months after first-line chemotherapy + bevacizumab start. The rate of bevacizumab interruption for progression or adverse drug reactions (ADRs) constituted the primary endpoint. Results: A total of 78.2% of patients interrupted bevacizumab: 56.6% for progression, 7.3% for ADRs, and 36.1% for other reasons. Median treatment duration was 6.7, 2.5, and 4.6 months, respectively. Median progression-free survival was 10.3 months; however, 35.8% of patients were not progressed and were thus censored at the data cutoff of 15 months, while 21.8% were still receiving bevacizumab. Patients discontinuing for progression/ADRs more frequently had metastases in >1 site ( p = .0001), and a shorter median progression-free survival (6.9 vs 13.9 months, p < .0001). Conclusions: In Italy, first-line bevacizumab is interrupted mainly for progression, only 7.3% due to adverse events, and about one third of cases for other reasons. In clinical practice, the attitude to treat until progression as per guidelines might be implemented. ClinicalTrials.gov Identifier: NCT01609075

Published
2019

3. Corrigendum: Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer (British Journal of Cancer (2016) 115 (789-796) DOI: 10.1038/bjc.2016.271)

Author

Dalgleish AG, Stebbing J, Adamson DJ, Arif SS, Bidoli P, Chang D, Cheeseman S, Diaz-Beveridge R, Fernandez-Martos C, Glynne-Jones R, Granetto C, Massuti B, McAdam K, McDermott R, Martín AJ, Papamichael D, Pazo-Cid R, Vieitez JM, Zaniboni A, Carroll KJ, Wagle S, Gaya A, Mudan SS., Dalgleish, A, Stebbing, J, Adamson, D, Arif, S, Bidoli, P, Chang, D, Cheeseman, S, Diaz-Beveridge, R, Fernandez-Martos, C, Glynne-Jones, R, Granetto, C, Massuti, B, Mcadam, K, Mcdermott, R, Martín, A, Papamichael, D, Pazo-Cid, R, Vieitez, J, Zaniboni, A, Carroll, K, Wagle, S, Gaya, A, and Mudan, S

Subjects
Gemcitabine
Abstract

Upon publication of the above paper in the British Journal of Cancer, the authors identified an error in one of their affiliations. The authors would like to apologise for this mistake. The correct affiliation for Andrés J Munoz Martín is 'Medical Oncology Service, Hospital General Universitario Gregorio Maranón, Madrid, Spain.'

Published
2016

4. FOLFOXIRI or FOLFOXIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: a propensity score-adjusted analysis from two randomized clinical trials.ANNALS OF ONCOLOGY, ISSN: 0923-7534

Author

Cremolini, C, Loupakis, F, Masi, G, Lonardi, S, Granetto, C, Mancini, Marialaura, Chiara, S, Moretto, R, Rossini, Daniela, Vitello, S, Allegrini, G, Tonini, G, Bergamo, F, Tomasello, G, Ronzoni, M, Buonadonna, A, Bustreo, S, Barbara, C, Boni, Maria Luisa, and Falcone, A. 1. 5.

Published
2016

5. Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) As First-Line Treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest

Author

Falcone, A., Ricci, S., Brunetti, I., Pfanner, E., Allegrini, G., Barbara, C., Crino, L., Benedetti, G., Evangelista, W., Fanchini, L., Cortesi, Enrico, Picone, V., Vitello, S., Chiara, S., Granetto, C., Porcile, G., Fioretto, L., Orlandini, C., Andreuccetti, M., Masi, G., and Ovest Gruppo Oncologico Nord

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, Leucovorin, Neutropenia, Irinotecan, Gastroenterology, Recurrence, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, Aged, FOLFOXIRI, business.industry, Middle Aged, medicine.disease, Survival Analysis, Surgery, Oxaliplatin, Oncology, Fluorouracil, Quality of Life, FOLFIRI, Camptothecin, Female, Colorectal Neoplasms, business, Febrile neutropenia, medicine.drug
Abstract

Purpose The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI). Methods Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR). Results A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032). Conclusion The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.

Published
2007

6. Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest

Author

Cremolini, C, Loupakis, F, Antoniotti, C, Lonardi, S, Masi, G, Salvatore, L, Cortesi, Enrico, Tomasello, G, Spadi, R, Zaniboni, A, Tonini, G, Barone, C, Vitello, S, Longarini, R, Bonetti, A, D&apos, Amico, M, Di Donato, S, Granetto, C, Boni, L, and Falcone, A.

Subjects
Adult, Oncology, Prognostic variable, medicine.medical_specialty, Time Factors, Organoplatinum Compounds, Bevacizumab, Colorectal cancer, Population, Leucovorin, Angiogenesis Inhibitors, Kaplan-Meier Estimate, Disease-Free Survival, early tumor shrinkage, depth of response, FOLFOXIRI, bevacizumab, Risk Factors, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoplasm Metastasis, education, Aged, Proportional Hazards Models, education.field_of_study, Univariate analysis, Chi-Square Distribution, business.industry, Proportional hazards model, Hematology, Middle Aged, medicine.disease, Tumor Burden, Treatment Outcome, Early tumor shrinkage, Italy, Multivariate Analysis, Disease Progression, FOLFIRI, Camptothecin, Fluorouracil, Colorectal Neoplasms, Depth of response, business, medicine.drug
Abstract

Background Early tumor shrinkage (ETS) and depth of response (DoR) predict overall survival (OS) in first-line trials of chemotherapy ± anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC). These associations and the predictive accuracy of response measurements for survival parameters were investigated in the phase III TRIBE trial of FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev. Patients and methods A landmark approach was adopted to define the assessable population. The distribution of RECIST response rate, ETS and DoR was compared in the two arms. Associations between response measurements and progression-free survival (PFS), post-progression survival (PPS) and OS were tested by univariate and multivariate Cox models. Prediction performance of each factor was estimated by C-index. Results A significantly higher percentage of patients in the FOLFOXIRI plus bev arm achieved ETS ≥20%, when compared with the control arm (62.7% versus 51.9%, P = 0.025). Also the DoR was significantly higher in the triplet plus bev arm (43.4% versus 37.8%, P = 0.003). Both ETS and DoR were associated with PFS, PPS and OS at the univariate analyses and in the multivariate models stratified for other prognostic variables. Both ETS and DoR were able to predict survival as accurately as RECIST response. Conclusion FOLFOXIRI plus bev improves ETS and DoR when compared with FOLFIRI plus bev. Achieving rapid and deep tumor shrinkage consistently delays tumor progression and prolongs survival in patients treated with first-line chemotherapy plus bev. ETS is a promising and valuable end point for clinical trials' design deserving further investigation.

Published
2015

7. Second-line chemotherapy (CT) with or without bevacizumab (BV) in metastatic colorectal cancer (mCRC) patients (pts) who progressed to a first-line treatment containing BV: Updated results of the phase III 'BEBYP'trial by the Gruppo Oncologico Nord Ovest (GONO)

Author

GIANLUCA MASI, Loupakis, F., Salvatore, L., CHIARA CREMOLINI, Fornaro, L., Schirripa, M., Granetto, C., Miraglio, E., Di Costanzo, F., Antonuzzo, L., Marcucci, L., Barbara, C., Boni, C., Banzi, M., Chiara, S., Garbarino, D., Valsuani, C., Bonetti, A., Boni, L., and Alfredo Falcone

Published
2013

8. A multicenter, randomized phase III study of second-line chemotherapy (CT) with or without bevacizumab (BV) in metastatic colorectal cancer (MCRC) patients who progressed to a first-line treatment containing bv: results from the bebyp trial by the Gruppo Oncologico Nord Ovest (GONO)

Author

Salvatore, L., GIANLUCA MASI, Loupakis, F., CHIARA CREMOLINI, Schirripa, M., Fornaro, L., Antoniotti, C., Vivaldi, C., Granetto, C., Fea, E., Antonuzzo, L., Giommoni, E., Boni, C., Banzi, M., Chiara, S., Sonaglio, C., Allegrini, G., Marcucci, L., Valsuani, C., Greco, F., Safina, V., Boni, L., and Alfredo Falcone

Published
2012

13. Phase III Trial of infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) compared with infusional Fluorouracil,Leucovorin, and Irinotecan (FOLFIRI) as first-line treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest(G.O.N.O.)

Author

Alfredo Falcone, Ricci, S., Brunetti, I., Pfanner, E., Allegrini, G., Barbara, C., Crin, L., Benedetti, G., Evangelista, W., Fanchini, L., Cortesi, E., Picone, V., Vitello, S., Chiara, S., Granetto, C., Porcile, G., Fioretto, L., Orlandini, C., Andreuccetti, M., and GIANLUCA MASI

Published
2007

25. Preoperative fluorouracil (FU)-based chemoradiation +/- weekly oxaliplatin in locally advanced rectal cancer. Pathologic response analysis of the star (Studio terapia adiuvante retto)-01 randomized phase III trial

Author

Aschele, C., Cionini, L., Carmine Pinto, Cordio, S., Rosati, G., Siena, S., Ambrosini, G., Pucciarelli, S., Rosetti, P., Niespolo, R., Granetto, C., Tassinari, D., Pasquini, E., Aitini, E., Tamberi, S., Falcone, A., Segati, R., Gaion, F., Petric, M., Lonardi, S., Gallo, M., Romeo, S., and Boni, L.

33. Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in older patients: A subgroup analysis from the TOSCA trial

Author

Gerardo Rosati, Sara Lonardi, Fabio Galli, Maria Di Bartolomeo, Monica Ronzoni, Maria G. Zampino, Maria Banzi, Alberto Zaniboni, Felice Pasini, Silvia Bozzarelli, Silvio K. Garattini, Daris Ferrari, Vincenzo Montesarchio, Andrea Mambrini, Libero Ciuffreda, Francesca Galli, Valeria Pusceddu, Chiara Carlomagno, Paolo Bidoli, Domenico Amoroso, Anna M. Bochicchio, Luca Frassineti, Domenico Corsi, Domenico Bilancia, Alessandro Pastorino, Alfonso De Stefano, Roberto Labianca, D. Bilancia, G. Rosati, V. Montesarchio, R.V. Iaffaioli, G. Nasti, B. Daniele, V. Zagonel, S. Lonardi, N. Pella, G. Aprile, F. Pasini, Roma P. Marchetti, A. Romiti, L. Ciuffreda, D. Ferrari, P. Foa, A. Zaniboni, R. Labianca, S. Mosconi, A. Sobrero, P. Bidoli, M. Cazzaniga, G.D. Beretta, D.C. Corsi, E. Cortesi, S. Barni, F. Petrelli, P. Allione, A.M. D'Arco, G. Valmadre, E. Piazza, E. Veltri, G. Vietti Ramus, L. Giustini, S. Tumulo, S. Cascinu, C. Granetto, F. Testore, M. Giordano, M. Moroni, M. Di Seri, A. Nuzzo, L. Angelelli, S. Gori, G. Farina, M. Aglietta, R. Franchi, M. Comandé, P. Giordani, G. Tonini, E. Bucci, A. Ballestrero, M. Benasso, C. Graiff, S. Bravi, O. Caffo, R.R. Silva, L. Frontini, S. Rota, L. Cozzi, M. Cantore, E. Maiello, S. Cinieri, N. Silvestris, S. Romito, V. Gebbia, M. Banzi, A. Santoro, F. Artioli, R. Mattioli, A. Contu, F. Di Costanzo, F. Leonardi, L. Cavanna, R. Passalacqua, D. Amoroso, P. Sozzi, M. D'Amico, D. Amadori, L. Frassineti, D. Turci, A. Ravaioli, E. Pasquini, A. Gambi, M. Faedi, G. Cruciani, E. Bajetta, M. Di Bartolomeo, L. Gianni, M. Ronzoni, M.T. Ionta, B. Massidda, M. Scartozzi, M.G. Zampino, A.M. Bochicchio, A. Ciarlo, A. Di Leo, S. Frustaci, G. Rangoni, A. Arizzoia, L. Pavesi, C. Verusio, G. Pinotti, A. Iop, S. De Placido, C. Carlomagno, V. Adamo, C. Ficorella, D. Natale, E. Greco, E. Rulli, F. Galli, D. Poli, L. Porcu, V. Torri, Rosati, G, Lonardi, S, Galli, F, Di Bartolomeo, M, Ronzoni, M, Zampino, M, Banzi, M, Zaniboni, A, Pasini, F, Bozzarelli, S, Garattini, S, Ferrari, D, Montesarchio, V, Mambrini, A, Ciuffreda, L, Pusceddu, V, Carlomagno, C, Bidoli, P, Amoroso, D, Bochicchio, A, Frassineti, L, Corsi, D, Bilancia, D, Pastorino, A, De Stefano, A, Labianca, R, Iaffaioli, R, Nasti, G, Daniele, B, Zagonel, V, Pella, N, Aprile, G, Marchetti, R, Romiti, A, Foa, P, Mosconi, S, Sobrero, A, Cazzaniga, M, Beretta, G, Cortesi, E, Barni, S, Petrelli, F, Allione, P, D'Arco, A, Valmadre, G, Piazza, E, Veltri, E, Ramus, G, Giustini, L, Tumulo, S, Cascinu, S, Granetto, C, Testore, F, Giordano, M, Moroni, M, Di Seri, M, Nuzzo, A, Angelelli, L, Gori, S, Farina, G, Aglietta, M, Franchi, R, Comande, M, Giordani, P, Tonini, G, Bucci, E, Ballestrero, A, Benasso, M, Graiff, C, Bravi, S, Caffo, O, Silva, R, Frontini, L, Rota, S, Cozzi, L, Cantore, M, Maiello, E, Cinieri, S, Silvestris, N, Romito, S, Gebbia, V, Santoro, A, Artioli, F, Mattioli, R, Contu, A, Di Costanzo, F, Leonardi, F, Cavanna, L, Passalacqua, R, Sozzi, P, D'Amico, M, Amadori, D, Turci, D, Ravaioli, A, Pasquini, E, Gambi, A, Faedi, M, Cruciani, G, Bajetta, E, Gianni, L, Ionta, M, Massidda, B, Scartozzi, M, Ciarlo, A, Di Leo, A, Frustaci, S, Rangoni, G, Arizzoia, A, Pavesi, L, Verusio, C, Pinotti, G, Iop, A, De Placido, S, Adamo, V, Ficorella, C, Natale, D, Greco, E, Rulli, E, Poli, D, Porcu, L, Torri, V, Rosati, G., Lonardi, S., Galli, F., Di Bartolomeo, M., Ronzoni, M., Zampino, M. G., Banzi, M., Zaniboni, A., Pasini, F., Bozzarelli, S., Garattini, S. K., Ferrari, D., Montesarchio, V., Mambrini, A., Ciuffreda, L., Pusceddu, V., Carlomagno, C., Bidoli, P., Amoroso, D., Bochicchio, A. M., Frassineti, L., Corsi, D., Bilancia, D., Pastorino, A., De Stefano, A., Labianca, R., Iaffaioli, R. V., Nasti, G., Daniele, B., Zagonel, V., Pella, N., Aprile, G., Marchetti, R. P., Romiti, A., Foa, P., Mosconi, S., Sobrero, A., Cazzaniga, M., Beretta, G. D., Cortesi, E., Barni, S., Petrelli, F., Allione, P., D'Arco, A. M., Valmadre, G., Piazza, E., Veltri, E., Ramus, G. V., Giustini, L., Tumulo, S., Cascinu, S., Granetto, C., Testore, F., Giordano, M., Moroni, M., Di Seri, M., Nuzzo, A., Angelelli, L., Gori, S., Farina, G., Aglietta, M., Franchi, R., Comande, M., Giordani, P., Tonini, G., Bucci, E., Ballestrero, A., Benasso, M., Graiff, C., Bravi, S., Caffo, O., Silva, R. R., Frontini, L., Rota, S., Cozzi, L., Cantore, M., Maiello, E., Cinieri, S., Silvestris, N., Romito, S., Gebbia, V., Santoro, A., Artioli, F., Mattioli, R., Contu, A., Di Costanzo, F., Leonardi, F., Cavanna, L., Passalacqua, R., Sozzi, P., D'Amico, M., Amadori, D., Turci, D., Ravaioli, A., Pasquini, E., Gambi, A., Faedi, M., Cruciani, G., Bajetta, E., Gianni, L., Ionta, M. T., Massidda, B., Scartozzi, M., Ciarlo, A., Di Leo, A., Frustaci, S., Rangoni, G., Arizzoia, A., Pavesi, L., Verusio, C., Pinotti, G., Iop, A., De Placido, S., Adamo, V., Ficorella, C., Natale, D., Greco, E., Rulli, E., Poli, D., Porcu, L., Torri, V., and Corsi, D. C.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Colorectal cancer, Leucovorin, Efficacy, Older patient, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Stage (cooking), Aged, 80 and over, Colonic Neoplasm, Prognostic factor, Middle Aged, Prognosis, Colon cancer, Survival Rate, Oxaliplatin, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, Fluorouracil, medicine.drug, Human, Compliance, Adult, medicine.medical_specialty, Prognosi, Adjuvant chemotherapy, Older patients, Prognostic factors, Subgroup analysis, Follow-Up Studie, 03 medical and health sciences, Internal medicine, Post-hoc analysis, medicine, Adjuvant therapy, Humans, Capecitabine, Cancer staging, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, medicine.disease, 030104 developmental biology, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

Published
2021

34. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial

Author

Chiara Cremolini, Carlotta Antoniotti, Daniele Rossini, Sara Lonardi, Fotios Loupakis, Filippo Pietrantonio, Roberto Bordonaro, Tiziana Pia Latiano, Emiliano Tamburini, Daniele Santini, Alessandro Passardi, Federica Marmorino, Roberta Grande, Giuseppe Aprile, Alberto Zaniboni, Sabina Murgioni, Cristina Granetto, Angela Buonadonna, Roberto Moretto, Salvatore Corallo, Stefano Cordio, Lorenzo Antonuzzo, Gianluca Tomasello, Gianluca Masi, Monica Ronzoni, Samantha Di Donato, Chiara Carlomagno, Matteo Clavarezza, Giuliana Ritorto, Andrea Mambrini, Mario Roselli, Samanta Cupini, Serafina Mammoliti, Elisabetta Fenocchio, Enrichetta Corgna, Vittorina Zagonel, Gabriella Fontanini, Clara Ugolini, Luca Boni, Alfredo Falcone, Filippo Guglielmo Maria De Braud, Evaristo Maiello, Giovanni Luca Frassineti, Teresa Gamucci, Francesco Di Costanzo, Luca Gianni, Patrizia Racca, Giacomo Allegrini, Alberto Sobrero, Massimo Aglietta, Enrico Cortesi, Domenico Cristiano Corsi, Alberto Ballestrero, Andrea Bonetti, Francesco Di Clemente, Enzo Ruggeri, Fortunato Ciardiello, Marco Benasso, Stefano Vitello, Saverio Cinieri, Stefania Mosconi, Nicola Silvestris, Antonio Frassoldati, Samantha Cupini, Alessandro Bertolini, Giampaolo Tortora, Carmelo Bengala, Daris Ferrari, Antonia Ardizzoia, Carlo Milandri, Silvana Chiara, Gianpiero Romano, Stefania Miraglia, Laura Scaltriti, Francesca Pucci, Livio Blasi, Silvia Brugnatelli, Luisa Fioretto, Angela Stefania Ribecco, Raffaella Longarini, Michela Frisinghelli, Maria Banzi, Cremolini, C., Antoniotti, C., Rossini, D., Lonardi, S., Loupakis, F., Pietrantonio, F., Bordonaro, R., Latiano, T. P., Tamburini, E., Santini, D., Passardi, A., Marmorino, F., Grande, R., Aprile, G., Zaniboni, A., Murgioni, S., Granetto, C., Buonadonna, A., Moretto, R., Corallo, S., Cordio, S., Antonuzzo, L., Tomasello, G., Masi, G., Ronzoni, M., Di Donato, S., Carlomagno, C., Clavarezza, M., Ritorto, G., Mambrini, A., Roselli, M., Cupini, S., Mammoliti, S., Fenocchio, E., Corgna, E., Zagonel, V., Fontanini, G., Ugolini, C., Boni, L., Falcone, A., De Braud, F. G. M., Maiello, E., Frassineti, G. L., Gamucci, T., Di Costanzo, F., Gianni, L., Racca, P., Allegrini, G., Sobrero, A., Aglietta, M., Cortesi, E., Corsi, D. C., Ballestrero, A., Bonetti, A., Di Clemente, F., Ruggeri, E., Ciardiello, F., Benasso, M., Vitello, S., Cinieri, S., Mosconi, S., Silvestris, N., Frassoldati, A., Bertolini, A., Tortora, G., Bengala, C., Ferrari, D., Ardizzoia, A., Milandri, C., Chiara, S., Romano, G., Miraglia, S., Scaltriti, L., Pucci, F., Blasi, L., Brugnatelli, S., Fioretto, L., Ribecco, A. S., Longarini, R., Frisinghelli, M., and Banzi, M.

Subjects
Male, 0301 basic medicine, GONO, Organoplatinum Compounds, multicentre, Leucovorin, Colorectal Neoplasm, Gastroenterology, Settore MED/06, Antineoplastic Agents, Immunological, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Metastasis, FOLFOXIRI, progression versus mFOLFOX6 plus bevacizumab, mFOLFOX6, metastatic colorectal cancer, Middle Aged, TRIBE2 trial, FOLFIRI plus bevacizumab, Neoplasm Metastasi, Bevacizumab, FOLFOXIRI plus bevacizumab, triplet FOLFOXIRI, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, Disease Progression, FOLFIRI, Female, metastatic colorectal cancer, triplet FOLFOXIRI , FOLFOXIRI plus bevacizumab, FOLFIRI plus bevacizumab, progression versus mFOLFOX6 plus bevacizumab, TRIBE2, Colorectal Neoplasms, Human, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Analogs & derivatives, open-label, NO, Young Adult, 03 medical and health sciences, Folinic acid, Internal medicine, medicine, cancer, Humans, neoplasms, Aged, Antineoplastic Combined Chemotherapy Protocol, Performance status, business.industry, Organoplatinum Compound, randomised controlled, FOLFOXIRI, bevacizumab, mFOLFOX6, FOLFIRI, metastatic colorectal cancer, TRIBE2 trial, multicentre, open-label, phase 3, randomised controlled, GONO, Irinotecan, 030104 developmental biology, phase 3, TRIBE2, Camptothecin, business
Abstract

Summary Background The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer, compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of therapies after disease progression. We aimed to compare a preplanned strategy of upfront FOLFOXIRI followed by the reintroduction of the same regimen after disease progression versus a sequence of mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI doublets, in combination with bevacizumab. Methods TRIBE2 was an open-label, phase 3, randomised study of patients aged 18–75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 2, with unresectable, previously untreated metastatic colorectal cancer, recruited from 58 Italian oncology units. Patients were stratified according to centre, ECOG performance status, primary tumour location, and previous adjuvant chemotherapy. A randomisation system incorporating a minimisation algorithm was used to randomly assign patients (1:1) via a masked web-based allocation procedure to two different treatment strategies. In the control group, patients received first-line mFOLFOX6 (85 mg/m2 of intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab (5 mg/kg intravenously over 30 min) followed by FOLFIRI (180 mg/m2 of intravenous irinotecan over 120 min concurrently with 200 mg/m2 of leucovorin; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab after disease progression. In the experimental group, patients received FOLFOXIRI (165 mg/m2 of intravenous irinotecan over 60 min; 85 mg/m2 intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 3200 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab followed by the reintroduction of the same regimen after disease progression. Combination treatments were repeated every 14 days for up to eight cycles followed by fluorouracil and leucovorin (at the same dose administered at the last induction cycle) plus bevacizumab maintenance until disease progression, unacceptable adverse events, or consent withdrawal. Patients and investigators were not masked. The primary endpoint was progression-free survival 2, defined as the time from randomisation to disease progression on any treatment given after first disease progression, or death, analysed by intention to treat. Safety was assessed in patients who received at least one dose of their assigned treatment. Study recruitment is complete and follow-up is ongoing. This trial is registered with Clinicaltrials.gov , NCT02339116 . Findings Between Feb 26, 2015, and May 15, 2017, 679 patients were randomly assigned and received treatment (340 in the control group and 339 in the experimental group). At data cut-off (July 30, 2019) median follow-up was 35·9 months (IQR 30·1–41·4). Median progression-free survival 2 was 19·2 months (95% CI 17·3–21·4) in the experimental group and 16·4 months (15·1–17·5) in the control group (hazard ratio [HR] 0·74, 95% CI 0·63–0·88; p=0·0005). During the first-line treatment, the most frequent of all-cause grade 3–4 events were diarrhoea (57 [17%] vs 18 [5%]), neutropenia (168 [50%] vs 71 [21%]), and arterial hypertension (25 [7%] vs 35 [10%]) in the experimental group compared with the control group. Serious adverse events occurred in 84 (25%) patients in the experimental group and in 56 (17%) patients in the control group. Eight treatment-related deaths were reported in the experimental group (two intestinal occlusions, two intestinal perforations, two sepsis, one myocardial infarction, and one bleeding) and four in the control group (two occlusions, one perforation, and one pulmonary embolism). After first disease progression, no substantial differences in the incidence of grade 3 or 4 adverse events were reported between the control and experimental groups, with the exception of neurotoxicity, which was only reported in the experimental group (six [5%] of 132 patients). Serious adverse events after disease progression occurred in 20 (15%) patients in the experimental group and 25 (12%) in the control group. Three treatment-related deaths after first disease progression were reported in the experimental group (two intestinal occlusions and one sepsis) and four in the control group (one intestinal occlusion, one intestinal perforation, one cerebrovascular event, and one sepsis). Interpretation Upfront FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression seems to be a preferable therapeutic strategy to sequential administration of chemotherapy doublets, in combination with bevacizumab, for patients with metastatic colorectal cancer selected according to the study criteria. Funding The GONO Cooperative Group, the ARCO Foundation, and F Hoffmann–La Roche.

Published
2020

35. Italian survey on cetuximab-based therapy of elderly patients with metastatic colorectal cancer

Author

Emanuela Dell'Aquila, Paolo Tralongo, Chiara Carlomagno, Stefano Cordio, Cristina Granetto, Antonio Di Stasi, Gabriella Buccafusca, Domenico Germano, Silvana Leo, Filippo Venturini, Tiziana Latiano, Maurizio Di Bisceglie, Antonio Avallone, Raffaele Addeo, Francesco Giuliani, Silvia Brugnatelli, Maria Elena Stroppolo, Salvatore Bianco, Giuseppe Aprile, Gerardo Rosati, Sara Delfanti, Domenico Bilancia, Samantha Di Donato, Rosati, G., Addeo, R., Aprile, G., Avallone, A., Bilancia, D., Brugnatelli, S., Buccafusca, G., Carlomagno, C., Cordio, S., Delfanti, S., Dell'Aquila, E., Di Bisceglie, M., Di Donato, S., Di Stasi, A., Germano, D., Giuliani, F., Granetto, C., Latiano, T. P., Leo, S., Tralongo, P., Stroppolo, M. E., Venturini, F., and Bianco, S.

Subjects
0301 basic medicine, Oncology, Male, Proto-Oncogene Proteins B-raf, Cancer Research, medicine.medical_specialty, Colorectal cancer, Cetuximab, Cancer Care Facilities, Toxicology, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Mutational status, Humans, Pharmacology (medical), Medical history, Neoplasm Metastasis, Survey, Geriatric Assessment, Aged, Pharmacology, Not evaluated, Aged, 80 and over, business.industry, Metastatic colorectal cancer, Geriatric assessment, medicine.disease, Diarrhea, 030104 developmental biology, Italy, 030220 oncology & carcinogenesis, Health Care Surveys, FOLFIRI, ras Proteins, Female, medicine.symptom, business, Colorectal Neoplasms, Elderly patient, medicine.drug
Abstract

Purpose There is no consensus on the use of cetuximab in elderly patients with metastatic colorectal cancer. To this end, a survey was carried in 17 Italian oncology centers. Methods The centers answered a 29-item questionnaire structured as follows: (i) demographic characteristics; (ii) medical history; (iii) assessment of RAS/BRAF mutations and DPD/UGT polymorphism before treatment; (iv) treatment schemes and side effects; (v) geriatric assessment and customization of treatment. Results One-third of patients are over 80 years old. The RAS/BRAF mutational status is not primarily evaluated by 17.6% of the centers, while DPD and UGT polymorphism is not evaluated by 82.4% and 76.5% of the centers. The most common therapeutic scheme is cetuximab/FOLFIRI and diarrhea is the main cause of suspension/reduction of treatment. The 70% of centers use systemic tetracyclines for skin toxicity. The 23.5% of the centers do not carry out any geriatric evaluation before the start of the therapy and those who perform it prefer the G8 (70.6%) and VES-13 (29.4%) scales. Conclusions Greater efforts should be made to improve the evaluation of the patient both about mutational and genetic procedures with geriatric evaluation. As for cetuximab in elderly patients, randomized studies are needed to provide guidance to physicians.

Published
2019

36. TRIPLETE: A randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer

Author

Gianluca Masi, Erika Martinelli, Angelo Martignetti, Chiara Cremolini, Alessandra Boccaccino, Nicoletta Pella, Cristina Granetto, Lorenzo Antonuzzo, Alessandro Passardi, Luca Boni, Valentina Angela Marsico, Carlotta Antoniotti, Francesca Vannini, Laura Delliponti, Camilla Colombo, Sara Lonardi, Gemma Zucchelli, Andrea Bonetti, Filippo Pietrantonio, Roberto Moretto, Francesco Leone, Valentina Burgio, Lisa Salvatore, Monica Di Battista, Stefano Vitello, Alfredo Falcone, Alberto Zaniboni, Daniele Rossini, Beatrice Borelli, Federica Marmorino, Borelli, B., Moretto, R., Lonardi, S., Bonetti, A., Antoniotti, C., Pietrantonio, F., Masi, G., Burgio, V., Marmorino, F., Salvatore, L., Rossini, D., Zaniboni, A., Zucchelli, G., Martignetti, A., Di Battista, M., Pella, N., Passardi, A., Boccaccino, A., Leone, F., Colombo, C., Granetto, C., Vannini, F., Marsico, V. A., Martinelli, E., Antonuzzo, L., Vitello, S., Delliponti, L., Boni, L., Cremolini, C., and Falcone, A.

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Cancer Research, Bevacizumab, Colorectal cancer, triplet, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, folfoxiri, medicine, Panitumumab, anti-EGFR monoclonal antibody, metastatic colorectal cancer, panitumumab, FOLFOXIRI, Cetuximab, business.industry, medicine.disease, digestive system diseases, Oxaliplatin, Irinotecan, Regimen, 030104 developmental biology, 030220 oncology & carcinogenesis, business, medicine.drug
Abstract

Background FOLFOXIRI plus bevacizumab is considered a standard option in the upfront treatment of clinically selected patients with metastatic colorectal cancer irrespective of RAS and BRAF molecular status. The randomised MACBETH and VOLFI studies showed that a modified FOLFOXIRI regimen in combination with cetuximab or panitumumab, respectively, achieved high therapeutic activity in RAS and BRAF wild-type patients with an acceptable toxicity profile. Drawing from these considerations, we designed TRIPLETE study aiming at comparing two different chemotherapy backbones (mFOLFOXIRI or mFOLFOX6) in combination with panitumumab in the first-line treatment of patients with RAS and BRAF wild-type metastatic colorectal cancer. Methods This is a prospective, open-label, multicentre phase III trial in which initially unresectable and previously untreated RAS and BRAF wild-type metastatic colorectal cancer patients are randomised to receive a standard treatment with mFOLFOX6 plus panitumumab or an experimental regimen with modified FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, L-leucovorin 200 mg/m2, 5-fluoruracil 2400 mg/m2 48-hour continuous infusion) plus panitumumab up to 12 cycles, followed by panitumumab plus 5-fluorouracil and L-leucovorin until disease progression. The primary endpoint is overall response rate according to RECIST 1.1 criteria. Discussion The relative benefit of chemotherapy intensification when using an anti-EGFR-based regimen in molecularly selected patients is unknown; TRIPLETE study aims at filling this gap of knowledge. The study is sponsored by the Gruppo Oncologico Nord Ovest Cooperative Group and is currently ongoing at 42 Italian centres. Clinical trial information NCT03231722.

Published
2018

37. Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer

Author

Kevin J Carroll, Demetris Papamichael, Douglas Adamson, Robert Diaz-Beveridge, Roberto Pazo-Cid, S. Arif, Rob Glynne-Jones, Angus Dalgleish, Sue Cheeseman, Paolo Bidoli, Andres J. Muñoz Martín, Carlos Fernández-Martos, Shama Wagle, Andrew Gaya, Raymond McDermott, Bartomeu Massuti, Karen McAdam, Alberto Zaniboni, D Chang, Justin Stebbing, Cristina Granetto, Satvinder Mudan, Jose M Vieitez, Cancer Research UK, Dalgleish, A, Stebbing, J, Adamson, D, Arif, S, Bidoli, P, Chang, D, Cheeseman, S, Diaz-Beveridge, R, Fernandez-Martos, C, Glynne-Jones, R, Granetto, C, Massuti, B, Mcadam, K, Mcdermott, R, Martín, A, Papamichael, D, Pazo-Cid, R, Vieitez, J, Zaniboni, A, Carroll, K, Wagle, S, Gaya, A, Mudan, S, and Action Against Cancer

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, endocrine system diseases, Colorectal cancer, FOLFIRINOX, pancreatic cancer, Phases of clinical research, Kaplan-Meier Estimate, GUIDELINES, Deoxycytidine, 0302 clinical medicine, IMM-101, advanced pancreatic ductal adenocarcinoma, Neoplasm Metastasis, Aged, 80 and over, gemcitabine, immunomodulator, Middle Aged, phase II, Combined Modality Therapy, Europe, Treatment Outcome, SAFETY, 030220 oncology & carcinogenesis, SURVIVAL, TRIAL, Female, immunotherapy, Open label, Corrigendum, Liver cancer, Life Sciences & Biomedicine, Carcinoma, Pancreatic Ductal, medicine.drug, Antimetabolites, Antineoplastic, medicine.medical_specialty, Cancer Vaccines, Disease-Free Survival, 03 medical and health sciences, Breast cancer, Mycobacterium obuense, Internal medicine, Pancreatic cancer, Biomarkers, Tumor, medicine, Humans, Oncology & Carcinogenesis, Lung cancer, Aged, Science & Technology, business.industry, Immunotherapy, Active, Cancer, ADENOCARCINOMA, medicine.disease, Gemcitabine, Pancreatic Neoplasms, 030104 developmental biology, Clinical Study, bacteria, business, 1112 Oncology And Carcinogenesis
Abstract

Background: Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. Methods: Patients were randomised (2 : 1) to IMM-101 (10 mg ml−l intradermally)+GEM (1000 mg m−2 intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. Results: IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44–1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33–0.87, P=0.01). Conclusions: IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study.

Published
2016

38. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study

Author

Alfredo Falcone, Chiara Cremolini, Luca Boni, Cristiana Lupi, Giacomo Allegrini, Marina Cazzaniga, Silvana Chiara, Chiara Carlomagno, Silvia Mezi, Sara Lonardi, Giuseppe Tonini, Carlotta Antoniotti, Gianluca Tomasello, Alberto Zaniboni, Gabriella Fontanini, Fotios Loupakis, Elisa Sensi, Monica Ronzoni, Cristina Granetto, Mauro D'Amico, Cremolini, C, Loupakis, F, Antoniotti, C, Lupi, C, Sensi, E, Lonardi, S, Mezi, S, Tomasello, G, Ronzoni, M, Zaniboni, A, Tonini, G, Carlomagno, Chiara, Allegrini, G, Chiara, S, D'Amico, M, Granetto, C, Cazzaniga, M, Boni, L, Fontanini, G, Falcone, A., Carlomagno, C, and Falcone, A

Subjects
Male, Oncology, Time Factors, Organoplatinum Compounds, Colorectal cancer, DNA Mutational Analysis, Leucovorin, Angiogenesis Inhibitors, Kaplan-Meier Estimate, chemotherapy, METASTATIC COLORECTAL, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Metastasis, FOLFOXIRI, unresectable metastatic colorectal cancer, RAS and BRAF, Middle Aged, Aged, Bevacizumab, Camptothecin, Colorectal Neoplasms, Disease-Free Survival, Drug Administration Schedule, Female, Fluorouracil, Humans, Infusions, Intravenous, Intention to Treat Analysis, Irinotecan, Italy, Mutation, Oxaliplatin, Proportional Hazards Models, Proto-Oncogene Proteins, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins p21(ras), Treatment Outcome, ras Proteins, FOLFIRI, Intravenous, medicine.drug, Infusions, medicine.medical_specialty, bevacizumab, Internal medicine, medicine, FOLFOXIRI plus bevacizumab, FOLFIRI plus bevacizumab, metastatic colorectal cancer, 3 TRIBE study, Performance status, business.industry, medicine.disease, business
Abstract

BACKGROUND: In the TRIBE study, FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab significantly improved progression-free survival of patients with metastatic colorectal cancer compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. In this updated analysis, we aimed to provide mature results for overall survival-a secondary endpoint-and report treatment efficacy in RAS and BRAF molecular subgroups. METHODS: TRIBE was an open-label, multicentre, phase 3 randomised study of patients (aged 18-70 years with Eastern Cooperative Oncology Group [ECOG] performance status of 2 or less and aged 71-75 years with an ECOG performance status of 0) with unresectable metastatic colorectal cancer who were recruited from 34 Italian oncology units. Patients were randomly assigned (1:1) via a web-based procedure to receive FOLFIRI plus bevacizumab or FOLFOXIRI plus bevacizumab. Bevacizumab was given as a 5 mg/kg intravenous dose. FOLFIRI consisted of a 180 mg/m2 intravenous infusion of irinotecan for 60 min followed by a 200 mg/m2 intravenous infusion of leucovorin for 120 min, a 400 mg/m2 intravenous bolus of fluorouracil, and a 2400 mg/m2 continuous infusion of fluorouracil for 46 h. FOLFOXIRI consisted of a 165 mg/m2 intravenous infusion of irinotecan for 60 min, followed by an 85 mg/m2 intravenous infusion of oxaliplatin given concurrently with 200 mg/m2 leucovorin for 120 min, followed by a 3200 mg/m2 continuous infusion of fluorouracil for 48 h. Tissue samples for RAS and BRAF mutational status analyses were centrally collected. In this updated analysis, we assessed the secondary endpoint of overall survival in the main cohort and treatment efficacy in RAS and BRAF molecular subgroups. All analyses were by intention to treat. TRIBE was concluded on Nov 30, 2014. The trial is registered with ClinicalTrials.gov, number NCT00719797. FINDINGS: Between July 17, 2008, and May 31, 2011, 508 patients were randomly assigned. At a median follow-up of 48·1 months (IQR 41·7-55·6), median overall survival was 29·8 months (95% CI 26·0-34·3) in the FOLFOXIRI plus bevacizumab group compared with 25·8 months (22·5-29·1) in the FOLFIRI plus bevacizumab group (hazard ratio [HR] 0·80, 95% CI 0·65-0·98; p=0·03). Median overall survival was 37·1 months (95% CI 29·7-42·7) in the RAS and BRAF wild-type subgroup compared with 25·6 months (22·4-28·6) in the RAS-mutation-positive subgroup (HR 1·49, 95% CI 1·11-1·99) and 13·4 months (8·2-24·1) in the BRAF-mutation-positive subgroup (HR 2·79, 95% CI 1·75-4·46; likelihood-ratio test p

Published
2015

39. Phase II study of sequential cisplatin plus 5-fluorouracil/leucovorin (5-FU/LV) followed by irinotecan plus 5-FU/LV followed by docetaxel plus 5-FU/LV in patients with metastatic gastric or gastro-oesophageal junction adenocarcinoma

Author

Lucia Mentuccia, E. Fontana, Marco Merlano, Lisa Salvatore, Alfredo Falcone, Lorenzo Fornaro, Fotios Loupakis, Stefano Cascinu, Giacomo Allegrini, Michele Andreuccetti, Enrico Cortesi, Gianluca Masi, Enrico Vasile, Cristina Granetto, Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori and Department of Oncology, Transplants and New Technologies in Medicine, University of Pisa - Università di Pisa, Unit of Medical Oncology, Istituto Toscano Tumori, Unit of Oncology, Azienda Ospedaliera S. Croce e Carle, Unit of Medical Oncology, Department of Experimental Medicine and Pathology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Unit of Medical Oncology, Azienda Ospedaliera Ospedali Riuniti, Università Politecnica delle Marche [Ancona] (UNIVPM), Loupakis, F., Masi, G., Fornaro, L., Vasile, E., Allegrini, G., Fontana, E., Granetto, C., Salvatore, L., Mentuccia, L., Andreuccetti, M., Cortesi, E., Merlano, M., Cascinu, S., and Falcone, A.

Subjects
Oncology, Male, Cancer Research, Esophageal Neoplasms, medicine.medical_treatment, Leucovorin, Phases of clinical research, Docetaxel, Toxicology, Gastroenterology, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Pharmacology (medical), Neoplasm Metastasis, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Middle Aged, 3. Good health, Treatment Outcome, Fluorouracil, Sequential chemotherapy, 030220 oncology & carcinogenesis, Female, Taxoids, Esophagogastric Junction, gastric cancer, sequential chemotherapy, irinotecan, docetaxel, cisplatin, 5-fluorouracil, medicine.drug, Adult, medicine.medical_specialty, 5-Fluorouracil, Neutropenia, Adenocarcinoma, Irinotecan, 03 medical and health sciences, Stomach Neoplasms, Internal medicine, medicine, Humans, 030304 developmental biology, Aged, Pharmacology, Chemotherapy, business.industry, medicine.disease, Concomitant, Camptothecin, Cisplatin, business, Gastric cancer, Febrile neutropenia
Abstract

5-Fluorouracil (5-FU) plus cisplatin (C) can be considered a standard option for advanced gastric cancer (AGC). Irinotecan (Ir) and docetaxel (D) are active agents with no complete cross-resistance with C and 5-FU. Concomitant combination of Ir or D with C and 5-FU is feasible, but with substantial toxicities. A different way to include all active agents in first-line treatment of AGC may be to use them sequentially. We aimed to evaluate the activity and the safety profile of sequential chemotherapy with 5-FU-based doublets with C, Ir and D in the first-line treatment of AGC. We conducted a phase II study of first-line sequential chemotherapy in metastatic GC. Treatment consisted of 3 cycles of C + infused 5-FU and leucovorin (CFL) followed by 3 cycles of Ir + 5-FU/LV (IrFL) followed by 3 cycles of D + 5-FU/LV (DFL). Primary end-point was response rate. Forty-six patients were enrolled, median age 60 years, sites of disease (single/multiple) = 9/37, PS 0/1 = 27/19, gastric/gastro-oesophageal junction = 39/7. Median number of cycles was 9. Main grade 3–4 toxicities were neutropenia (37%), febrile neutropenia (2%), diarrhoea (4%), stomatitis (9%). Response rate after the planned 9 cycles was 45% (15 partial and 5 complete responses among 43 evaluable patients). Median PFS and OS: 6.8 and 11.1 months, respectively. This sequential treatment is feasible with a favourable safety profile and produced encouraging results in terms of activity and efficacy.

Published
2010

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