Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab.
| Title | Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Koutras, A. K., Antonacopoulou A. G., Eleftheraki A. G., Dimitrakopoulos F-I., Koumarianou A., Varthalitis I., Fostira F., Sgouros J., Briasoulis E., Bournakis E., Bafaloukos D., Bompolaki I., Galani E., Kalogeras K. T., Pectasides D., Fountzilas G., & Kalofonos H. P. |
| Journal | Pharmacogenomics J |
| Volume | 12 |
| Issue | 6 |
| Pagination | 468-75 |
| Date Published | 2012 Dec |
| ISSN | 1473-1150 |
| Keywords | Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Colorectal Neoplasms, Female, Genotype, Humans, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Vascular Endothelial Growth Factor A |
| 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. |
| DOI | 10.1038/tpj.2011.37 |
| Alternate Journal | Pharmacogenomics J. |
| PubMed ID | 21844885 |
