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• W79025227 abstract "4633 CYP2A6 genetic polymorphism as a predictive marker for clinical outcomes in patients (pts) with metastastic gastric carcinoma (MGC) treated with S-1 plus docetaxel Background: Tegafur, a component of S-1, a novel oral fluoropyrimidine, is converted to 5-fluorouracil via CYP2A6. An allelic variant of CYP2A6, -48T>G (CYP26A*9) encodes an enzyme with reduced activity. We investigated the association between the polymorphism of CYP2A6*9 and treatment outcomes in Korean pts with MGC who received S-1 plus docetaxel. Methods: From Oct 2005 to July 2006, 50 pts with MGC were enrolled for a phase II study of first line chemotherapy with S-1 and docetaxel. Treatment consisted of oral S-1 40 mg/m 2 bid on days 1–14, and i.v. docetaxel 35 mg/m 2 on days 1, 8, every 3 weeks. Genotypes were determined with single base extension method for CYP26A*9 from genomic DNA extracted from the peripheral blood samples. Results: The median age was 53 years (range, 23–70) with the median PS of 1 (range, 0–2). The frequency of wild type allele (w/w) was 34 (68%), heterozygous (*9/w), 12 (24%), and homozygous (*9/*9), 4 (8%). The response rate was 25.0% in homozygous pts, 50.0% in heterozygous and 76.5% in wild type (p=0.03, Fisher’s exact test). The median time to progression at a median follow-up of 9.8 months (mo) was shorter in homozygous pts (3.9 mo; 95% CI, 0.4–7.4) as compared to heterozygous and wild types (6.9 mo; 95% CI, 6.0–7.8) (p=0.11). Although the median overall survival did not reach in 4 homozygous pts, it was 13.5 mo (95% CI, 8.3–18.7) in heterozygous and wild type. The frequencies of grade (G) 3/4 toxicities were lower in homozygous pts than the others without statistical significance. Conclusions: The data suggest that CYP2A6*9 polymorphism might be a predictive marker for efficacy and toxicity of S-1 based chemotherapy in MGC pts. Further studies involving more pts are needed to confirm the results. (Supported by NCC Grant 0610520) [Table: see text] No significant financial relationships to disclose." @default.
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• W79025227 date "2007-06-20" @default.
• W79025227 modified "2023-09-24" @default.
• W79025227 title "CYP2A6 genetic polymorphism as a predictive marker for clinical outcomes in patients (pts) with metastastic gastric carcinoma (MGC) treated with S-1 plus docetaxel" @default.
• W79025227 doi "https://doi.org/10.1200/jco.2007.25.18_suppl.4633" @default.
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