Fiche publication
Date publication
octobre 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BEDENNE Laurent
,
Pr BOUCHE Olivier
Tous les auteurs :
Manfredi S, Bouche O, Rougier P, Dahan L, Loriot MA, Aparicio T, Etienne PL, Lafargue JP, Lecaille C, Legoux LL, Le Malicot K, Maillard E, Lecomte T, Khemissa F, Breysacher G, Michel P, Mitry E, Bedenne L
Lien Pubmed
Résumé
High-dose FOLFIRI has an acceptable safety profile and a promising efficacy. UDP-glucuronosyltransferase: (UGT1A1) polymorphism may be predictive of toxicity and efficacy of irinotecan. This phase II study aimed to evaluate the combination of high-dose FOLFIRI plus bevacizumab in patients with previously untreated metastatic colorectal cancer (MCRC) based on their UGT1A1 genotype. Patients with the UGT1A1 *1/*1 (group 1) or *1/*28 (group 2) genotype received bevacizumab plus high-dose FOLFIRI every 2 weeks. Using the Bryant and Day design with objective response rate and toxicity as the primary endpoints, 54 pts (patients) in each group was required with a planned interim analysis after inclusion of 17 pts per group. We planned to stop the trial at the interim analysis if /= 3 pts exhibited severe toxicity. At the interim analysis, ORs were higher than the number expected: 52.9% (group 1) and 58.8% (group 2). More than 3 toxic events occurred in both groups and, according to the interim analysis rule, the trial was closed due to unacceptable toxicity. Recruitment was stopped when 86 pts were included and an analysis on overall population was done for overall survival (OS) and progression-free survival (PFS). The median PFS was 10.7 months (group 1), 10.4 months (group 2). The median OS was 25.5 months (group 1), 23.9 months (group 2). This trial does not support the use of the intensive treatment with HD-FOLFIRI plus bevacizumab combination for MCRC in patients with the UGTA1*1/UGT1A1*1 or UGT1A1*1/UGT1A1*28 genotype.
Référence
Mol Cancer Ther. 2015 Oct 22. pii: molcanther.0293.2015.
