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Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2017, Vol.20 (1), p.146-155
Associations between CYP2A6 polymorphisms and outcomes of adjuvant S-1 chemotherapy in patients with curatively resected gastric cancer
Ist Teil von
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2017, Vol.20 (1), p.146-155
Ort / Verlag
Tokyo: Springer Japan
Erscheinungsjahr
2017
Quelle
EZB-FREE-00999 freely available EZB journals
Beschreibungen/Notizen
Background
Oral fluoropyrimidine S-1 contains tegafur, which is metabolized to 5-fluorouracil by cytochrome P450 2A6 (CYP2A6). We here examined associations between
CYP2A6
polymorphisms and treatment outcomes of adjuvant S-1 in gastric cancer patients.
Methods
Patients received adjuvant S-1 (40 mg/m
2
twice daily, days 1–28, every 6 weeks for eight cycles) after curative surgery for pathological stage II–III gastric cancer. We analyzed the wild-type allele (W) (
CYP2A6*1
) and four variant alleles (V) (
CYP2A6*4
,
*7
,
*9
,
*10
) that abolish or reduce this enzyme activity.
Results
Patients (
n
= 200) were enrolled between November 2007 and July 2013 with the following clinical characteristics: median age, 57 years (range, 32–83 years); 128 men, 72 women. With a median follow-up of 46.4 months, the 3-year relapse-free survival (RFS) and overall survival (OS) rates were 83.1 % (95 % CI, 77.7–88.5 %) and 94.8 % (95 % CI, 91.6–98.0 %), respectively. Genotype distributions were as follows:
W/W
(
n
= 49, 24.5 %),
W/V
(
n
= 94, 47.0 %), and
V/V
(
n
= 57, 28.5 %). Overall toxicity did not differ according to genotype for any grade (
p
= 0.612) or grade ≥3 (
p
= 0.143). However, RFS differed significantly according to
CYP2A6
genotype. The 3-year RFS rates were 95.9 % for
W/W
, 83.1 % for
W/V
, and 72.5 % for
V/V
(
p
= 0.032). Carriers of
W/V
and
V/V
genotypes had a poorer RFS with a hazard ratio of 3.41 (95 % CI, 1.01–11.52;
p
= 0.049) and 4.03 (95 % CI, 1.16–13.93;
p
= 0.028), respectively, compared with the
W/W
genotype.
Conclusions
CYP2A6
polymorphisms are not associated with toxicity of S-1 chemotherapy, but correlate with the efficacy of S-1 in the adjuvant setting for gastric cancer.