奥沙利铂与氟尿嘧啶类药物基因多态性对晚期胃肠癌患者疗效和不良反应影响的真实世界研究

A real-world study on the effects of gene polymorphism and chemotherapy regimen of oxaliplatin and fluorouracil on patients with advanced gastrointestinal cancer

目的:探究晚期胃肠癌患者基因多态性与化疗疗效及不良反应之间的关系。方法:选取2020年4月1日至2022年6月30日期间皖南医学院第一附属医院收治的89例接受奥沙利铂联合氟尿嘧啶类药物(氟尿嘧啶、替吉奥和卡培他滨)化疗的晚期胃肠癌患者,探究氟尿嘧啶类药物选择和药物基因多态性与短期疗效和不良反应之间的关联性。结果:本研究未观测到DPYD基因突变;MTHFR(677 C>T)基因野生型30例、突变型46例,突变时白细胞和粒细胞减少发生率显著升高(P=0.031和P=0.043);GSTP1(313 A>G)野生型56例、突变型26例,突变时血红蛋白减少发生率显著降低(P=0.019)。氟尿嘧啶在癌胚抗原下降程度(氟尿嘧啶vs.替吉奥vs.卡培他滨=4.83 vs. 0.00 vs.-0.27)和客观缓解率(氟尿嘧啶vs.替吉奥vs.卡培他滨=47.1%vs. 21.1%vs. 19.4%)方面存在显著优势;相较于氟尿嘧啶和卡培他滨,替吉奥所致肝功能异常发生率相对更低(P=0.002),但血红蛋白减少发生率明显更高(P=0.009);而氟尿嘧啶引起白细胞和血小板减少发生率较替吉奥和卡培他滨更低(P=0.001和P=0.020)。结论:胃肠癌患者化疗前筛查GSTP1(313 A>G)和MTHFR(677 C>T)基因可能有助于奥沙利铂联合氟尿嘧啶类药物的个体化治疗药物选择,而用药前DPYD基因型检测的必要性可能需更大样本的临床研究验证。

OBJECTIVE To study the association between gene polymorphism and chemotherapy efficacy and adverse reactions of patients with advanced gastrointestinal cancer.METHODS From April 1,2020 to June 30,2022,89 patients with advanced gastrointestinal cancer who received oxaliplatin combined with fluorouracil(fluorouracil,S-1 and capecitabine)chemotherapy in the First Affiliated Hospital of Wannan Medical College were selected.The associations between fluorouracil drug selection,drug gene polymorphism and short-term efficacy,adverse reactions were compared.RESULTS No mutation of DPYD gene was observed in this study.There were 30 cases of wild type and 46 cases of mutant type of MTHFR(677C>T).The incidence of leukopenia and granulocytopenia was significantly increased during mutation(P=0.031 and P=0.043).There were 56 cases of wild type of GSTP1(313A>G)and 26 cases of mutation,and the incidence of hemoglobin reduction decreased significantly(P=0.019).Fluorouracil showed obvious advantages in the reduction degree of carcinoembryonic antigen(5-fluorouracil vs.S-1 vs.capecitabine=4.83 vs.0.00 vs.-0.27)and objective remission rate(5-fluorouracil vs.S-1 vs.capecitabine=47.1%vs.21.1%vs.19.4%).Compared with 5-fluorouracil and capecitabine,the incidence of hepatic dysfunction caused by S-1 was relatively lower(P=0.002),but the incidence of hemoglobin reduction was significantly higher(P=0.009),while the incidence of leukopenia and thrombocytopenia caused by fluorouracil was relatively lower than that caused by S-1 and capecitabine(P=0.001 and P=0.020).CONCLUSION Screening GSTP1(313A>G)and MTHFR(677C>T)before chemotherapy may be helpful to the individual drug selection of oxaliplatin combined with fluorouracil,and the necessity of DPYD genotype testing before medication may need to be verified by clinical research with larger samples.