Efficacy and safety of bevacizumab-based combination regimens in patients with previously untreated metastatic colorectal cancer: Final results from a randomised phase ii study of bevacizumab plus 5-fluorouracil, leucovorin plus irinotecan versus bevacizumab plus capecitabine plus irinotecan (FNCLCC ACCORD 13/0503 study)

M. Ducreux, A. Adenis, J. P. Pignon, E. François, B. Chauffert, J. L. Ichanté, E. Boucher, M. Ychou, J. Y. Pierga, C. Montoto-Grillot, T. Conroy

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    Résumé

    Background: The combination of bevacizumab and bolus 5-fluorouracil, leucovorin and irinotecan is highly effective in patients with metastatic colorectal cancer (mCRC). This randomised, multicenter, non-comparative phase II trial assessed the efficacy and safety of bevacizumab plus oral capecitabine plus irinotecan (XELIRI) or infusional 5-fluorouracil, leucovorin plus irinotecan (FOLFIRI) as first-line therapy for patients with mCRC. Patients and Methods: Patients received bevacizumab 7.5 mg/kg on day 1 plus XELIRI (irinotecan 200 mg/m2 on day 1 and oral capecitabine 1000 mg/m 2 bid on days 1-14) every 3 weeks or bevacizumab 5 mg/kg on day 1 plus FOLFIRI (5-fluorouracil 400 mg/m2 on day 1 plus 2400 mg/m 2 as a 46-h infusion, leucovorin 400 mg/m2 on day 1, and irinotecan 180 mg/m2 on day 1) every 2 weeks. Patients aged ≥65 years received a lower dose of capecitabine (800 mg/m2 twice daily). The primary endpoint was 6-month progression-free survival (PFS) rate. Results: A total of 145 patients were enrolled (bevacizumab-XELIRI, n = 72; bevacizumab-FOLFIRI, n = 73). The 6-month PFS rate was 82% (95% confidence intervals (CI) 71-90%) in the bevacizumab-XELIRI arm and 85% (95% CI 75-92%) in the bevacizumab-FOLFIRI arm. In both the bevacizumab-XELIRI and bevacizumab-FOLFIRI arms, median PFS and overall survival (OS) were 9 and 23 months, respectively. The most frequent toxicities were grade 3/4 neutropenia (bevacizumab-XELIRI 18%; bevacizumab-FOLFIRI 26%) and grade 3 diarrhoea (12% and 5%, respectively). Conclusions: This randomised non-comparative study demonstrates that bevacizumab-XELIRI and bevacizumab-FOLFIRI are effective regimens for the first-line treatment of patients with mCRC with manageable toxicity profiles.

    langue originaleAnglais
    Pages (de - à)1236-1245
    Nombre de pages10
    journalEuropean Journal of Cancer
    Volume49
    Numéro de publication6
    Les DOIs
    étatPublié - 1 avr. 2013

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