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


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).


CONCLUSIONS
Our findings showed that the CYP2A6 genotype correlated with the treatment efficacy of S-1-based chemotherapy in previously untreated metastatic gastric cancer patients.
Kong
Sun-Young
SY
Research Institute & Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea.
Lim
Hyeong-Seok
HS
Nam
Byung-Ho
BH
Kook
Myeong-Cherl
MC
Kim
Young-Woo
YW
Ryu
Keun Won
KW
Lee
Jun Ho
JH
Choi
Il Ju
IJ
Lee
Jin Soo
JS
Park
Young-Iee
YI
Kim
Noe Kyeong
NK
Park
Sook Ryun
SR
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065637:Cytochrome P-450 CYP2A6; D000077143:Docetaxel; D004338:Drug Combinations; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods / Q000639:trends; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D010865:Pilot Projects; D011110:Polymorphism, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary*; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
D004338:Drug Combinations; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6