Background: ERCC1 is an excision nuclease involved in the repair of platinum-DNA adducts. The purpose of this study was to evaluate the association between the C8092A polymorphisms in ERCC1 and progression-free survival (PFS) or overall survival (OS) in women with epithelial ovarian cancer (EOC) treated with cisplatin and paclitxel.
Methods: Women who were evaluable for the phase III protocol, GOG-172, and had sufficient leukocyte DNA for testing were eligible for this study. Participants were randomized to intraperitoneal (IP) vs. intravenous (IV) chemotherapy with cisplatin and paclitaxel. Single nucleotide polymorphism (SNP) analysis was evaluated by direct pyrosequencing.
Results: Among the 233 eligible cases, the distribution of ERCC1 genotypes at C8092A was 56% with C/C, 37% with C/A and 7% with A/A. Median age at enrollment was 57 years, 91.9% were Caucasian, 76.9% had serous adenocarcinoma, and 59.4% had macroscopic-residual disease <1 cm. Adjusted Cox regression analysis revealed that women with the C/A or A/A genotype compared with the C/C genotype at C8092A had an increased risk of disease progression (hazard ratio [HR]=1.48, 95% confidence interval [CI]=1.09-2.00, p=0.011) and death (HR=1.46, 95% CI=1.04-2.04, p=0.029). Subset analysis stratified by treatment suggested that the C8092A polymorphism was significantly associated with increased risk of PFS and OS in the IP but not the IV arm.
Conclusion: The C8092A polymorphism in ERCC1 appears to be an independent predictor of PFS and OS with optimally-resected EOC treated with cisplatin-paclitaxel chemotherapy. The preferential clinical utility of the C8092A polymorphism in those given IP vs. IV therapy requires validation.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA