UNASSIGNED: 3578 Background: The combination of high-dose @entity2600 (260mg/m(2)) with LV5FU2 (FOLFIRI @entity2033 regimen) is feasible with an acceptable safety profile and promising efficacy data (Ducreux et al. Oncology 2008;74:17-24). The aim of this phase II study was to evaluate the combination of FOLFIRI @entity2033 plus bevacizumab (B) in @entity1 (pts) selected on the @entity6912 polymorphism, which could be predictive of the @entity2600 @entity137 and efficacy. METHODS: Pts with @entity6912 *1/*1 (group 1) or *1/*28 (group 2) genotypes and previously untreated mCRC were treated with bevacizumab 5 mg/kg D1, @entity2600 260 mg/m   D1, LV 400 mg/m   D1, @entity1487 400 mg/m   IV bolus D1 and 5FU 2400 mg/m   46h infusion D1-2 every 2 weeks. Using Bryant _ Day design with objective response rate (ORR) (independent review, H0 <=  40%; H1 >=  60%) and @entity137 (gr 4 @entity1398 or @entity1398 or gr 3-4 @entity294 ; H0 >=  20%; H1<=  5%) as primary endpoints; a total of 108 pts, 54 in each group, was required (alpha 5% and power 80%) with a planned interim analysis after the inclusion of 17 pts by group. The trial will be stopped at interim analysis if <=  7 pts had an OR and/or >=  3 pts had a severe @entity137 . All analyses were performed in ITT. RESULTS: At the time of interim analysis, done when the 17th pt of group 1 had a 6-months follow-up, 86 pts were included (group 1: 40 pts, group 2: 46 pts). Results of primary endpoints at the interim analysis are presented in the table. According to interim analysis rules, the trial was closed to inclusion for unacceptable @entity137 . CONCLUSIONS: The trial was stopped after interim analysis because of unacceptable @entity137 according to @entity195 , even if @entity137 was manageable and most of the @entity1 continued the treatment after dose adaptation. Defined @entity137 criteria to stop the trial at interim analysis may have been too strict and not clinically adapted. There is however no clear benefit of the FOLFIRI @entity2033 - B combination in terms of efficacy. [Table: see text].

Phase II trial of chemotherapy with high-dose FOLFIRI plus bevacizumab in the front-line treatment of @entity1 with metastatic colorectal cancer (mCRC) and genotype @entity6912 *1/ XXXX *1 or @entity6912 *1/ @entity6912 *28 (FFCD 0504 trial): Final results.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity6912 :: ('54658', 'Gene') :: ['UGT1A1'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity2600 :: ('MESH:C051890', 'Chemical') :: ['irinotecan'] @entity294 :: ('MESH:D003967', 'Disease') :: ['diarrhea'] @entity2033 :: ('MESH:D006816', 'Disease') :: ['HD'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenia', 'febrile neutropenia'] @entity195 :: ('MESH:D000544', 'Disease') :: ["trial's criteria"] @entity1487 :: ('MESH:D005472', 'Chemical') :: ['5FU']
@entity6912 :: (54658,Gene) :: ['UGT1A1']
