Abstract 3689: Association of thymidylate synthase gene polymorphisms with efficacy and toxicity of oral fluoropyrimidine based chemotherapy in advanced gastric cancer

Abstract

Abstract Purpose: Oral fluoropyrimidines (S-1 or capecitabine) are metabolized by different enzymes. We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6), carboxylesterase 2(CES 2), thymidylate synthase (TS), and excision repair cross complementation group 1 (ERCC1) and toxicity of advanced gastric cancer patients treated with oral fluoropyrimidine based chemotherapy. Methods: A total of 123 patients received S-1 80mg/m2 or capecitabine 2000 mg/m2 plus oxaliplatin 130 mg/m2 for advanced gastric cancer. We analyzed polymorphisms of CYP2A6, CES 2, TS and ERCC1 by using genomic DNA extracted from prospectively collected peripheral blood sample. Associations between polymorphisms and toxicity of these patients treated with oral fluoropyrimidines based chemotherapy were evaluated individually. Results: Patients who were 2R/3R for the double repeat in the TS promoter region had more toxicity of oral fluoropyrimidines. Patients with a 2R/3R and 2R/2R or 3R/3R genotype had a grade 2 or more gastrointestinal toxicity rate of 50 and 22%, respectively (P = .049). Response rate was higher in patients with a 2R/3R than those with a 2R/2R or 3R/3R (50% vs. 32%, P = .082). Polymorphisms of CYP2A6, CES 2, and ERCC1 were not associated with efficacy and toxicity of oral fluoropyrimidine based chemotherapy for advanced gastric cancer. Conclusion. This study demonstrated that TS genotyping could be of help in predicting toxicity to oral fluoropyrimidine based chemotherapy in advanced gastric cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3689. doi:1538-7445.AM2012-3689