【作者】 朱利娜；

【导师】 杨振君；

【作者基本信息】 中国医科大学 ， 情报学， 2010， 硕士

【摘要】 背景与目的表皮生长因子受体酪氨酸激酶抑制剂(EGFR TKIs)吉非替尼和厄洛替尼,是新型非小细胞肺癌(NSCLC)分子靶向治疗药。有研究证明具有某些生物学和临床特性的患者对吉非替尼和厄洛替尼有更大的生存获益,但这些研究所得结论并不一致。本研究将收集所有吉非替尼和厄洛替尼与安慰剂对比治疗NSCLC的随机对照试验(RCT),并对数据进行Meta-分析,以评估生物学和临床特性对吉非替尼和厄洛替尼疗效的影响,筛选出优势人群。材料与方法计算机检索Cochrane图书馆临床对照试验库、Pubmed、Embase、CBM、CNKI、Wanfang Date等电子数据库,手工检索肿瘤相关的国内外会议论文集。对符合纳入标准的RCT进行质量评价和资料提取,采用Stata10软件进行统计分析。结果纳入8个RCT研究。从不吸烟者对吉非替尼和厄洛替尼有较大获益[生存期MST,不吸烟者：HR=0.52,95%CI(0.31,0.86)；吸烟者：HR=0.91,95%CI(0.81,1.02)；疾病进展期PFS,不吸烟者：HR=0.55,95%CI(0.42,0.72)；吸烟者：HR=0.89,95%CI(0.78,1.01)；肿瘤反应率RR,不吸烟者：OR=27.58,95%CI(5.40,140.72)；吸烟者：OR=4.57,95%CI(2.07,10.07)]; EGFR基因表达阳性者实验组死亡风险低于对照组[MST,HR=0.79,95%CI(0.65,0.97)]; EGFR基因拷贝数高的患者,实验组的疾病进展风险低于对照组[HR=0.55,95%CI(0.40,0.75)]；EGFR(19,20)基因突变者在肿瘤反应率上有明显优势[RR,OR=4.08,95%CI(1.14,14.68)]；K-ras突变者实验组的死亡风险[HR=1.97,95%CI(1.16,3.33)]和疾病进展风险[HR=1.90,95%CI(1.05,3.44)]均高于对照组。结论基于目前可获得的证据,只能证明不吸烟者是吉非替尼和厄洛替尼的优势人群,而K-ras突变者不适合接受吉非替尼和厄洛替尼治疗。对吉非替尼和厄洛替尼优势人群的筛选,仍需大量的前瞻性研究来证明。更多还原

【Abstract】 Epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKIs)-gefitinib and erlotinib is a targeted therapy drug for non-small cell lung cancer(NSCLC). There was evidence of a greater survival benefit from gefitinib and erlotinib in patients with certain molecular and clinical features, but results are conflicting. The aim of this study is to assess the role of these factors in gefitinib and erlotinib efficacy.Materials and methodsA systematic review of all the relevant randomized(RCTs) was performed. Searches were applied to the following electronic database:Cochrane Library, Pubmed, Embase, CBM, CNKI and Wanfang Date, and add hand search. The included studies, we performed assessment of studies quality and data extraction. StatalO software was used for meta-analysis.ResultsEight RCTs were analyzed. Non-smokers get more benefit from gefitinib and erlotinib [Median Survival Time(MST), Non smokers:HR=0.52,95%CI(0.31,0.86); Smokers:HR=0.91,95%CI(0.81,1.02);Progression-free survival(PFS), Non smokers: HR=0.55,95%CI(0.42,0.72); Smokers:HR=0.89,95%CI(0.78,1.01); Reponse Rate(RR), Non smokers:OR=27.58,95%CI(5.40,140.72); Smokers:OR=4.57, 95%CI(2.07,10.07)]; Patients with positive EGFR expression had a lower relative risk of death[MST, HR=0.79,95%CI(0.65,0.97)]; There was a positive effect of TKIs on PFS in patients whose tumours had a high EGFR gene copy number[HR=0.55, 95%CI(0.40,0.75)]; Patients with positive EGFR(19,21) mutations are benefit on RR[OR=4.08,95%CI(1.14,14.68)]; K-ras mutations are unfit for TKIs [MST, K-ras+ HR=1.97,95%CI(1.16,3.33);PFS,K-ras+:HR=1.90,95%CI(1.05,3.44)].ConclusionBased on the present evidence, non-smokers get more benefit from gefitinib and erlotinib, and K-ras mutations are unfit for gefitinib and erlotinib. Results of prospective randomized trials are awaited.更多还原