晚期非小细胞肺癌患者CYP2D6*10基因多态性与多西他赛疗效及安全性分析  

Analysis of CYP2D6*10 gene polymorphism and the efficacy and safety of docetaxel in patients with advanced non-small cell lung cancer

作　　者：吴昊[1] 焦子晗 张率然 吴沛鸿 董航 徐玲[1] WU Hao;JIAO Zi-han;ZHANG Shuai-ran;WU Pei-hong;DONG Hang;XU Ling(Department of Medical Oncology,First Hospital of China Medical University,Shenyang 110001,China)

机构地区：[1]中国医科大学附属第一医院肿瘤内科,辽宁沈阳110001

出　　处：《中华肿瘤防治杂志》2021年第16期1220-1225,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(81673025)。

摘　　要：目的分析CYP2D6*10基因多态性与应用多西他赛治疗的晚期非小细胞肺癌(NSCLC)患者疗效及安全性的相关性。方法选取2013-01-01-2018-10-31就诊于中国医科大学附属第一医院肿瘤内科且完善多基因检测的晚期NSCLC患者53例为研究对象,收集患者CYP2D6*10基因多态性状态、性别、年龄、是否吸烟、表皮生长因子受体(EGFR)状态、美国东部肿瘤协作组(ECOG)评分、无进展生存期(PFS)、总生存期(OS)以及不良反应等。分析CYP2D6*10基因多态性与患者疗效以及安全性关系。结果 53例患者中CYP2D6*10野生型34例(37.7%),纯合突变型7例(13.2%),杂合突变型12例(22.6%)。CYP2D6*10野生型患者中位OS为26个月,高于纯合突变型的21个月和杂合突变型的24个月,但差异无统计学意义,χ^(2)=0.835,P=0.659,95%CI为24.65~38.63。CYP2D6*10野生型患者PFS为4个月,高于纯合突变型的2个月和杂合突变型的2个月,差异无统计学意义,χ^(2)=5.908,P=0.052,95%CI为3.85~5.54。将CYP2D6*10纯合突变型和杂合突变型患者合为一组,患者PFS为2个月,CYP2D6*10野生型患者PFS为4个月,组间差异有统计学意义,χ^(2)=5.904,P=0.015,95%CI为3.85~5.54。Cox回归分析显示,CYP2D6*10基因多态性状态可作为PFS的独立预测因素,HR=1.962,95%CI为1.083~3.553,P=0.026。在不良反应方面,有11例患者发生>Ⅲ度骨髓抑制,其中8例(72.7%)发生在CYP2D6*10野生型患者中。结论应用多西他赛治疗的晚期NSCLC患者中,CYP2D6*10野生型PFS高于纯合突变型和杂合突变型患者。但本研究缺乏正常人对照,观察到的CYP2D6*10野生型患者可能更容易发生中重度血液学毒性的现象尚需进一步验证。Objective To investigate the association between CYP2 D6*10gene polymorphism and efficacy and safety in patients with advanced non-small cell lung cancer(NSCLC)treated with docetaxel.Methods This study screened 53patients with advanced NSCLC as research object who were diagnosed with multi-gene detection in the Department of Oncology of First Hospital of China Medical University from January 1,2013to October 31,2018.Data such as the polymorphism status of CYP2 D6*10,gender,age,smoking status,epidermal growth factor receptor(EGFR)status,Eastern Cooperative Oncology Group(ECOG)score,progression-free survival(PFS),overall survival(OS)and the occurrence of adverse events in patients were all collected.The correlation between the CYP2 D6*10genetic polymorphisms and efficacy and safety of patients was analyzed.Results Of the 53patients included in the study,34 (37.7%)were wild type CYP2 D6*10,7(13.2%)were homozygous mutants,and 12(22.6%)were heterozygous mutants.In terms of survival analysis,the median OS of CYP2 D6*10 wild-type patients was 26 months,higher than that of homozygous mutants(21months)and heterozygous(24months).The difference was not statistically significant(χ^(2)=0.835,P=0.659,95%CI:24.65-38.63).In terms of PFS,CYP2 D6*10wild-type patients were 4months,higher than that of the homozygous mutant 2months and the heterozygous(2months),and the difference was not statistically significant(χ^(2)=5.908,P=0.052,95%CI:3.85-5.54).When the CYP2 D6*10homozygous and heterozygous mutants patients were merged into one group,the PFS was 2months.However,the PFS of CYP2 D6*10wild type was 4months,and the difference between the groups was statistically significant(χ^(2)=5.904,P=0.015,95%CI:3.85-5.54),suggesting that wild-type patients may have longer PFS.Cox regression analysis showed that the polymorphisms status of CYP2 D6*10gene could be used as an independent predictor of PFS(HR=1.962,95%CI:1.083-3.553,P=0.026).In terms of adverse reactions,11patients had gradeⅢor higher myelosuppression,and 8of them(72.7%)occurre

关 键 词：CYP2D6*10基因多态性 晚期非小细胞肺癌 多西他赛 疗效 不良反应 

分 类 号：R734.2[医药卫生—肿瘤]