Abstract
The aim of the study was to evaluate the association of vascular endothelial growth factor (VEGF) genotypes with treatment efficacy in a randomized trial. This study compared two chemotherapy regimens (FOLFIRI versus XELIRI) combined with bevacizumab, as first-line treatment for metastatic colorectal cancer. DNA was extracted from blood samples of 173 patients participating in the trial. Genotyping was performed for selected SNPs (VEGF−1154, +936, −634, −2578 and −1498). All candidate genotypes were evaluated for associations with overall survival (OS), progression-free survival (PFS) and response rate (RR). There were no significant differences with respect to the distribution of genotypes in the treatment groups. The VEGF−1154 GG genotype was more frequent in patients not responding to treatment compared with responders (65.5 versus 39.8%, P=0.032). Furthermore, the VEGF−1154 GG genotype was associated with inferior median OS compared with GA (hazards ratio=1.68; 95% confidence interval: 1.10–2.57; P=0.016) or with the alternative genotypes (GA and AA) combined (hazards ratio=1.62; 95% confidence interval: 1.09–2.40; P=0.017). In multivariate analysis, the VEGF−1154 GG genotype remained a significant adverse factor for OS. Our results support the potential predictive ability of VEGF genotypes in patients with metastatic colorectal cancer receiving irinotecan-based chemotherapy plus bevacizumab, in terms of RR and OS. However, current results should be validated prospectively, in larger cohorts.
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Funding source: The study was supported by a Hellenic Cooperative Oncology Group (HeCOG) research grant (HE TR_10).
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Koutras, A., Antonacopoulou, A., Eleftheraki, A. et al. Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab. Pharmacogenomics J 12, 468–475 (2012). https://doi.org/10.1038/tpj.2011.37
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DOI: https://doi.org/10.1038/tpj.2011.37
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