Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab.
Pharmacogenomics J
; 12(6): 468-75, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-21844885
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Polimorfismo de Nucleotídeo Único
/
Fator A de Crescimento do Endotélio Vascular
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Pharmacogenomics J
Ano de publicação:
2012
Tipo de documento:
Article