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Associations between CYP2A6 polymorphisms and outcomes of adjuvant S-1 chemotherapy in patients with curatively resected gastric cancer
- Source :
- Gastric Cancer. 20:146-155
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- 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. Patients received adjuvant S-1 (40 mg/m2 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. 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. 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.
- Subjects :
- Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_treatment
Gastroenterology
Cytochrome P-450 CYP2A6
0302 clinical medicine
Genotype
CYP2A6
Aged, 80 and over
Hazard ratio
General Medicine
Middle Aged
Prognosis
Adenocarcinoma, Mucinous
Survival Rate
Drug Combinations
Chemotherapy, Adjuvant
030220 oncology & carcinogenesis
Toxicity
Female
Adjuvant
medicine.drug
Adult
Antimetabolites, Antineoplastic
medicine.medical_specialty
Real-Time Polymerase Chain Reaction
Tegafur
03 medical and health sciences
Gastrectomy
Stomach Neoplasms
Internal medicine
Biomarkers, Tumor
medicine
Humans
Aged
Neoplasm Staging
Retrospective Studies
Chemotherapy
Polymorphism, Genetic
business.industry
Cancer
medicine.disease
Oxonic Acid
030104 developmental biology
business
Carcinoma, Signet Ring Cell
Follow-Up Studies
Subjects
Details
- ISSN :
- 14363305 and 14363291
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Gastric Cancer
- Accession number :
- edsair.doi.dedup.....15788b50f792b21859f4590c1f9b7759