Association of CYP2A6 polymorphisms with S-1 plus docetaxel therapy outcomes in metastatic gastric cancer

摘要

Aims: S-1, an oral fluoropyrimidine, contains tegafur, which is converted to 5-fluorouracil mainly by CYP2A6. We evaluated the association between CYP2A6 polymorphisms and treatment outcome in metastatic gastric cancer patients treated with S-1 plus docetaxel. Materials & methods: Chemonaive patients received S-1 40 mg/m2 twice daily on days 1–14 and docetaxel 35 mg/m2 on days 1 and 8 of a 3-week cycle. We analyzed the wild-type (W) allele (CYP2A6*1) and four variant (V) alleles that abolish or reduce enzyme activity (CYP2A6*4, *7, *9 and *10). A total of 50 patients were enrolled. Results: The genotype frequencies were as follows: W/W (n = 14, 28%), W/V (n = 26, 52%) and V/V (n = 10, 20%). Patients having fewer variant alleles had significantly better response rates (W/W vs W/V vs V/V = 79 vs 65 vs 30%; p = 0.04) and median progression-free survival (W/W vs W/V vs V/V = 8.1 vs 6.9 vs 3.1 months; p = 0.0009). Conclusion: Our findings showed that the CYP2A6 genotype correlated with the treatment efficacy of S-1-based chemotherapy in previously untreated metastatic gastric cancer patients.