title: Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab.
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.
authors.affiliation: Department of Medicine, Division of Oncology, University Hospital of Patras, Rion, Greece. angkoutr@otenet.gr
authors.forename: A K
authors.initials: AK
authors.lastname: Koutras
authors.forename: A G
authors.initials: AG
authors.lastname: Antonacopoulou
authors.forename: A G
authors.initials: AG
authors.lastname: Eleftheraki
authors.forename: F-I
authors.initials: FI
authors.lastname: Dimitrakopoulos
authors.forename: A
authors.initials: A
authors.lastname: Koumarianou
authors.forename: I
authors.initials: I
authors.lastname: Varthalitis
authors.forename: F
authors.initials: F
authors.lastname: Fostira
authors.forename: J
authors.initials: J
authors.lastname: Sgouros
authors.forename: E
authors.initials: E
authors.lastname: Briasoulis
authors.forename: E
authors.initials: E
authors.lastname: Bournakis
authors.forename: D
authors.initials: D
authors.lastname: Bafaloukos
authors.forename: I
authors.initials: I
authors.lastname: Bompolaki
authors.forename: E
authors.initials: E
authors.lastname: Galani
authors.forename: K T
authors.initials: KT
authors.lastname: Kalogeras
authors.forename: D
authors.initials: D
authors.lastname: Pectasides
authors.forename: G
authors.initials: G
authors.lastname: Fountzilas
authors.forename: H P
authors.initials: HP
authors.lastname: Kalofonos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D005260:Female; D005838:Genotype; D006801:Humans; D000077146:Irinotecan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin