Pharmacogenomics. 2009 Jul;10(7):1147-55. doi: 10.2217/pgs.09.48.

Association of CYP2A6 polymorphisms with S-1 plus docetaxel therapy outcomes 

in metastatic gastric cancer.

Kong SY, Lim HS, Nam BH, Kook MC, Kim YW, Ryu KW, Lee JH, Choi IJ, Lee JS, Park YI, Kim NK, Park SR.

Abstract

AIMS:

S-1, an oral fluoropyrimidine, contains tegafur, which is converted to 5-fluorouracil mainly by CYP2A6. We evaluated the associationbetween 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.