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- Title
Retrospective exploratory analysis of VEGF polymorphisms in the prediction of benefit from first-line FOLFIRI plus bevacizumab in metastatic colorectal cancer.
- Authors
Loupakis, Fotios; Ruzzo, Annamaria; Salvatore, Lisa; Cremolini, Chiara; Masi, Gianluca; Frumento, Paolo; Schirripa, Marta; Catalano, Vincenzo; Galluccio, Nadia; Canestrari, Emanuele; Vincenzi, Bruno; Santini, Daniele; Bencardino, Katia; Ricci, Vincenzo; Manzoni, Mariangela; Danova, Marco; Tonini, Giuseppe; Magnani, Mauro; Falcone, Alfredo; Graziano, Francesco
- Abstract
Background: Molecular predictors of bevacizumab efficacy in colorectal cancer have not been identified yet. Specific VEGF polymorphisms may affect gene transcription and therefore indirectly influence the efficacy of bevacizumab. Methods: Genomic DNA of 111 consecutive metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab was obtained from blood samples. VEGF -2578 C/A, -1498 C/T, + 405 C/G, + 936 C/T polymorphisms were analyzed by means of PCR-RFLP. DNA samples from 107 patients treated with FOLFIRI alone served as historical control group. The relation of VEGF polymorphisms with PFS, evaluated through Kaplan-Meier method and log-rank test, was the primary end-point. An interaction test with a Cox model has been performed in order to demonstrate the heterogeneity of the effect of VEGF -1498 C/T polymorphism between bevacizumab-and control group. Results: In the bevacizumab-group median PFS and OS of patients carrying VEGF -1498 C/C, C/T and T/T allelic variants were, respectively, 12.8, 10.5, 7.5 months (p = 0.0046, log-rank test) and 27.3, 20.5, 18.6 months (p = 0.038, log-rank test). VEGF -1498 T/T genotype was associated with shorter PFS (HR = 2.13, [1.41-5.10], p = 0.0027). In the control group no significant association of VEGF -1498 C/T allelic variants and PFS or OS was found. Interaction between VEGF -1498 C/T variants and treatment effect suggested that the relation of VEGF -1498 T/T genotype with shorter PFS was caused by the effect of bevacizumab (p = 0.011). Other investigated polymorphisms did not affect the outcome. Conclusions: These data suggest a possible role for VEGF -1498 C/T variants in predicting the efficacy of bevacizumab in the up-front treatment of metastatic colorectal cancer patients. A molecular tool for selecting subjects candidate to benefit from the anti-VEGF could be important for clinical practice. The retrospective and exploratory design of the present study, coupled with the non-randomized nature of the comparison between treated and untreated patients, imply that these results should be considered as hypothesis generators. A prospective validating trial is currently ongoing.
- Subjects
COLON cancer; GENETIC polymorphisms; BEVACIZUMAB; DNA; TUMORS
- Publication
BMC Cancer, 2011, Vol 11, Issue 1, p247
- ISSN
1471-2407
- Publication type
Article
- DOI
10.1186/1471-2407-11-247