中国药房2017，Vol.28Issue(32)：4465-4470,6.DOI:10.6039/j.issn.1001-0408.2017.32.01
CYP3A4*18基因多态性与初治晚期NSCLC患者EGFR-TKI疗效及不良反应的相关性分析
Relationship Analysis of CYP3A4*18 Gene Polymorphism with Therapeutic Efficacy and ADR of EGFR-TKI in Advanced NSCLC Patients Receiving Primary Treatment
摘要
Abstract
OBJECTIVE:To investigate the relationship of Cytochrome P450 (CYP)3A4* 18 gene polymorphism with therapeutic efficacy and ADR of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients receiving primary treatment.METHODS:A total of 46 advanced NSCLC patients receiving primary EGFR-TKI (gefitinib or edotinib) treatment until disease progression or intolerance were selected from our hospital during Jan.2013-Mar.2016,and (gefitinib of erlotinib) treatment until disease progression or intolerance.CYP3A4*18 genotype was detected by PCR and direct sequencing.Clinical efficacies,progression-free survival (PFS) and the occurrence of ADR were compared among differ ent genotypes.RESULTS:Among 46 patients,there were 17 cases of CYP3A4*18 wild-type and 29 cases of CYP3A4*18 mutation-type,with mutation frequency of 63.0％.The objective response rate (ORR) of CYP3A4*18 wild-type patients was 23.5％,and disease control rate (DCR) of them was 70.6％.For CYP3A4*18 mutation-type patients,ORR and DCR were 27.6％ and 69.0％.There was no statistical significance in the proportion of patients with partial response,stable disease or progressive dis ease,ORR or DCR among different genotypes (P＞0.05).PFS of female patients were significantly longer than male patients;those of patients without smoking history were significantly longer than those with smoking history,with statistical significance (P＜0.05).There was no correlation between patients' age,therapy drugs,Eastern Oncology Collaboration scores,EGFR mutation types,CYP3A4*18 genotypes and PFS (P＞0.05).Patients'gender and smoking history were independent prognostic factors for PFS [odds ratios were 3.438,0.205,95％ CI were(1.393,8.488),(0.088,0.481)].Among CYP3A4* 18 wild-type patients,6 patients suffered from rash (35.3％) and 3 diarrhea (17.6％).Among mutation-type patients,26 patients suffered from rash (89.7％) and 15 diarrhea (51.7％),with statistical significance (P＜0.05).There was no statistical significance in the incidence of liver function injury and interstitial dermatitis among different genotypes (P＞0.05).CONCLUSIONS:CYP3A4*18 gene polymorphism may be not associated with therapeutic efficacy of EGFR-TKI in advanced NSCLC patients receiving primary treatment,but it is correlated with the occurrence of ADR.Mutation type patients are more likely to suffered from rash,diarrhea and other ADR.关键词
CYP3A4*18基因/多态性/晚期非小细胞肺癌/表皮生长因子受体酪氨酸激酶抑制剂/疗效/不良反应/相关性Key words
CYP3A4*18 gene/Polymorphism/Advanced non-small cell lung cancer/Epidermal growth factor receptor tyrosine kinase inhibitor/ADR/Relationship分类
医药卫生引用本文复制引用
程艳芳,王艳娜,王慧,孟玲利,巩平..CYP3A4*18基因多态性与初治晚期NSCLC患者EGFR-TKI疗效及不良反应的相关性分析[J].中国药房,2017,28(32):4465-4470,6.基金项目
国家自然科学基金资助项目(No.81560381) （No.81560381）
吴阶平医学基金会临床科研专项资助基金课题(No.320.6750.14269) （No.320.6750.14269）
