摘要
目的:S-1(替吉奥)的活性前体为替加氟,主要通过细胞色素P450酶2A6(human cytochrome P450,family 2,subfamily A,polypeptide 6,CYP2A6)代谢为5-FU而发挥细胞毒作用。本研究探讨CYP2A6基因多态性与胃癌术后患者含S-1辅助化疗方案疗效的相关性。方法:选取2007年11月至2013年5月于郑州市人民医院收治的胃癌患者200例,给予标准给药方案。在CYP2A6基因分析中,选取野生型的CYP2A6*1,突变型的CYP2A6*4、*7、*9、*10等位点进行分析。结果:200例患者中位随访时间为46.4(12.5~80.1)个月。野生型(W/W)3年无复发生存(relapse free survival,RFS)率为95.9%、突变杂合子(W/V)型为83.1%、突变纯合子(V/V)型为72.5%(P=0.032)。不同基因型之间的3~4级不良反应的差异无统计学意义(P=0.628,P=0.227)。结论:CYP2A6基因型与含S-1化疗方案的长期疗效有关,突变型患者的3年RFS降低。
Objective： Oral fluoropyrimidine S-1 contains tegafur, gimeracil, and oteracil; among them, tegafur is the major active pre- cursor, which is metabolized to 5-fluorouracil by cytochrome P4502A6 （CYP2A6）. We examined the associations between CYP2A6 poly- morphisms and the treatment outcomes of adjuvant S-1 in patients with gastric cancer. Methods： Two hundred patients diagnosed with pathological stage Ⅱ -Ⅲ gastric cancer were included in this study, and they received adjuvant S-1 （40 mg/m2, bid, days 1-28, ev- ery 6 weeks for eight cycles） after curative surgery. Additionally, we analyzed the wild-type allele （W） （CYP2A6＊1） and four variant alleles （V） （CYP2A6＊4, ＊7, ＊9, and ＊10）. Results： Two hundred patients were enrolled in this study between November 2007 and July 2013. With a median follow-up of 46.4 months （range： 12.5-80.1）, the 3-year relapse-free survival （RFS） and overall survival （OS） rates were 83.1% （95% confidence interval （Cl）, 77.7%-88.5%） and 94.8% （95% CI, 91.6%-98.0%4 respectively. However, RFS differed signifi cantly according to the CYP2A6 genotype. The 3-year RFS rates were 95.9% for W/W, 83.2% for W/V, and 72.5% for V/V （P=0.032） gen- otypes. Grades 3 and 4 overall toxicity did not differ according to genotype for any grade （P=0.628 and P=0.227, respectively）. Conclusions： CYP2A6 genotypes correlate with the outcome of S-2 chemotherapy, wherein patients with the variant genotypes show worse prognosis. Additionally, polymorphism detection may be used as a biomarker to guide clinical chemotherapy choices for adjuvant administration of gastric cancer therapy.
作者
刘桂举
梅家转
李瑞君
李伟娟
Guiju Liu, Jiazhuan Mei, Ruijun Li, Weijuan Li(Department of Oncology, People＇s Hospital of Zhengzhou, Zhengzhou 450000, Chin)
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2018年第4期171-178,共8页
Chinese Journal of Clinical Oncology
