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

BMC Research Notes

Jacques Robert²  Marianne Fonck⁷  Simone Mathoulin-Pélissier²  Caroline Lalet⁵  Sofiane Aitouferoukh³  René Brunet⁷  Dominique Béchade⁷  Valérie Le Morvan³  Patrick Texereau¹  Richard Beyssac⁴  Marina Pulido⁸  Laurent Cany⁶  Yves Bécouarn⁷ 

[1] Centre Hospitalier Layné, Mont de Marsan, France;Univ. Bordeaux, F-33000 Bordeaux, France;INSERM U916, Institut Bergonié, Comprehensive Cancer Centre, 229 cours de l’Argonne, F-33000 Bordeaux, France;Maison de Santé Protestante Bagatelle, Talence, France;Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Centre, 229 cours de l’Argonne, F-33000 Bordeaux, France;Polyclinique Francheville, Périgueux, France;Department of Digestive Oncology, Institut Bergonié, Comprehensive Cancer Centre, 229 cours de l’Argonne, F-33000 Bordeaux, France;CIC-EC7 (Clinical Investigation Centre – Clinical Epidemiology), Bordeaux, France

关键词: FOLFIRI® protocol;    Colorectal neoplasms;    Clinical trial, phase II;    Chemotherapy;    Bevacizumab;   

Others  :  1133259
DOI  :  10.1186/1756-0500-7-260

 received in 2014-03-26, accepted in 2014-04-03,  发布年份 2014

【 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/m²), 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)

【 授权许可】

   
2014 Bécouarn et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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