FOLFIRI® and Bevacizumab in first-line treatment for colorectal cancer patients: Safety, efficacy and genetic polymorphisms

被引：14

作者：

Bécouarn Y. ^{[1
]}

Cany L. ^{[2
]}

Pulido M. ^{[3
,4
]}

Beyssac R. ^{[5
]}

Texereau P. ^{[6
]}

Le Morvan V. ^{[7
]}

Béchade D. ^{[1
]}

Brunet R. ^{[1
]}

Aitouferoukh S. ^{[7
]}

Lalet C. ^{[3
]}

Mathoulin-Pélissier S. ^{[3
,8
]}

Fonck M. ^{[1
]}

Robert J. ^{[7
,8
]}

机构：

[1] Department of Digestive Oncology, Institut Bergonié, Comprehensive Cancer Centre, F-33000 Bordeaux

[2] Polyclinique Francheville, Périgueux

[3] Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Centre, F-33000 Bordeaux

[4] CIC-EC7 (Clinical Investigation Centre - Clinical Epidemiology), Bordeaux

[5] Maison de Santé Protestante Bagatelle, Talence

[6] Centre Hospitalier Layné, Mont de Marsan

[7] INSERM U916, Institut Bergonié, Comprehensive Cancer Centre, F-33000 Bordeaux

[8] Univ. Bordeaux

来源：

BMC Research Notes | / 7卷 / 1期

关键词：

Bevacizumab; Chemotherapy; Clinical trial phase II; Colorectal neoplasms; FOLFIRI®; protocol;

D O I：

10.1186/1756-0500-7-260

中图分类号：

学科分类号：

摘要：

Background: Over 50% of colorectal cancer (CRC) patients develop metastases. The aim of this study was to evaluate efficacy and tolerance of first-line FOLFIRI® + bevacizumab (B) treatment for metastatic CRC, and to assess genetic polymorphisms as potential markers. Methods. Adult patients with histologically-proven, non-resectable metastatic CRC and ECOG ≤ 2 were included. 14-day cycles consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m2), bolus FU (400 mg/m2) and leucovorin (400 mg/m 2), followed by 46-hour FU infusions (2400 mg/m2). Primary endpoint was response rate according to RECIST criteria. Secondary endpoints were overall (OS) and progression-free (PFS) survivals, response duration, and toxicity. Associations between clinical data, UGT1A1, thymidylate synthase, VEGFA polymorphisms and PFS, OS and toxicity were analyzed. Results: Sixty-two patients were enrolled (median age 68y). 59/62 patients were eligible and evaluable for response at 6 months: 28 showed partial response (47.5%; 95% CI; 34.3-60.9), 20 stable disease (33.9%) and 11 progression (18.6%). Grade 3/4 toxicities were as follows: neutropenia 16.1%; diarrhea 11.3%; nausea-vomiting 1.6%. Median response duration was 9.5 months (range 2.7-20); median PFS 10.3 months (range 8.8-11.7); and median OS 25.7 months (range 20.2-29.7). 11/59 initially unresectable patients were resectable after treatment. VEGFA polymorphism (rs25648) was associated with better OS (HR: 3.61; 95% CI: 1.57-8.30). Conclusions: FOLFIRI® + bevacizumab is active with good response rate, long median OS, and a good safety profile. A VEGFA polymorphism might have a prognostic value in this malignancy. Trial registration. Clinicaltrials.gov: NCT00467142 (registration date: April 25, 2007). © 2014 Bécouarn et al.; licensee BioMed Central Ltd.

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