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/m(2) twice daily on days 1-14 and docetaxel 35 mg/m(2) 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=0, 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.