Pharmacogenetic prediction of clinical outcome in gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

Abstract

e14506 Background: Many findings have been reported on the effect of polymorphisms of ERCC1, XRCC1, XPD, and GSTP1 genes on the response to platinum-based chemotherapy in various types of solid tumors. The aim of this study was to determine whether these molecular parameters could be partly responsible for sensitivity to oxaliplatin (OX)-based chemotherapy used as adjuvant treatment in resected gastric cancer. Methods: 126 resected gastric cancer patients received OX/5-fluorouracil chemotherapeutic regimen. Genetic polymorphisms of ERCC1-118, XRCC1-399,XPD-751, and GSTP1-105 were determined by the TaqMan 5′nuclease assay, using DNA from peripheral blood. Relapse-free survival (RFS) and overall survival (OS) were evaluated according to each genotype. Results: In the univariate analysis, ERCC1-118 and XRCC1-399 polymorphisms were significant for RFS (p<0.001 and p=0.001, respectively) and OS (p<0.001). After adjustment for the most relevant clinical variables, only ERCC1-118 retained significance for RFS (p<0.001) and OS (p<0.001) in the multivariate Cox survival analysis. Conclusions: Our data suggested that gastric cancer patients harboring ERCC1-118 C/C genotype and XRCC1-399 A/G or G/G genotypes may better receive oxaliplatin-based adjuvant chemotherapy. Hazard ratios for relapse-free survival and overall survival in patients receiving surgery followed by oxaliplatin-based adjuvant chemotherapy Prognostic factors RFS OS HR 95%CI p value HR 95% CI p value ERCC-118 <0.001 <0.001 C/C 1 1 C/T+T/T 2.501 1.560-4.009 2.478 1.505-4.080 Staging <0.001 <0.001 I + II + III 1 1 IV 3.328 2.120-5.225 3.027 1.846-4.962 Carcinoembryonic antigen 0.001 0.001 ≤ 5 ng/ml 1 1 > 5 ng/ml 2.228 1.373-3.614 2.521 1.496-4.251 Abbreviations: RFS, relapse-free survival; OS, overall survival; HR, hazard ratio. No significant financial relationships to disclose.