何伟+程淼

[摘要] 為评价中药联合第一代EGFR-TKI治疗中晚期非小细胞肺癌的有效性及安全性，检索中国生物医学文献数据库（CBM）、中国期刊全文数据库（CNKI）、维普期刊全文数据库（VIP）、Pubmed、CochraneLibrary、EMbase等中英文数据库，纳入中药联合第一代EGFR-TKI治疗中晚期非小细胞肺癌的随机对照临床试验研究，结局指标为总缓解率、疾病控制率、生活质量评分、1年生存率、不良反应/事件，采用Revman 5.3.5合并统计效应量，采用Stata 12.0分析潜在文献发表偏倚。共纳入17篇文献，计1 391例患者，试验组706例，对照组685例。研究质量较低，同质性较好，发表偏倚风险较小。Meta分析结果显示，中药联合第一代EGFR-TKI治疗中晚期非小细胞肺癌的总缓解率[RR=1.33，95%CI（1.17，1.51）]、疾病控制率[RR=1.21，95%CI（1.13，1.29）]、生活质量改善[RR=1.28，95%CI（1.17，1.41）]、1年生存率[RR=1.27，95%CI（1.01，1.61）]等有效性指标，优于单用第一代EGFR-TKI，均具有统计学差异（P<0.05）。且其皮肤毒性反应[RR=0.74，95%CI（0.63，0.86）]、胃肠道反应[RR=0.54，95%CI（0.41，0.71）]、肝功能损害[RR=0.41，95%CI（0.26，0.67）]等不良反应/事件的发生率，低于单用第一代EGFR-TKI，具有显著统计学差异（P<0.01）。Begg秩相关法检验显示不存在文献发表偏倚。总之，与单用第一代EGFR-TKI比较，联合中药治疗具有更好的有效性及安全性，但由于纳入研究样本量小，低质量多，研究结论仍需大样本高质量研究进一步验证。

[关键词] 中医药；EGFR-TKI；非小细胞肺癌；系统评价；Meta分析

[Abstract] To evaluate the efficacy and safety of traditional Chinese medicine combined with first-generation EGFR-TKI in treating advanced non-small cell lung cancer （NSCLC）. China biomedical literature database （CBM）， China Journal Full-text Database （CNKI）， VIP， PubMed， CochraneLibrary， EMbase and other Chinese and English databases were searched for randomized and clinical controlled trials of traditional Chinese medicine combined with first-generation EGFR-TKI in treating advanced NSCLC. The statistical effect was measured by Revman 5.3.5 based on the outcome indexes of total response rate， disease control rate， quality of life， one-year survival rate， and adverse reactions/events. Meanwhile， a bias risk assessment was conducted by Stata12.0. A total of 17 studies were included， involving 1 391 cases， with 706 cases in the treatment group and 685 cases in the control group. The studies featured a low methodological quality， high homogeneity and low publication bias risk. The meta-analysis showed that total response rate [RR=1.33， 95%CI （1.17， 1.51）]， disease control rate [RR=1.21， 95%CI （1.13， 1.29）]， quality of life improvement rate [RR=1.28， 95%CI （1.17， 1.41）]， one-year survival rate [RR=1.27， 95%CI （1.01， 1.61）]， and other indexes of effectiveness of Chinese medicine combined with first-generation EGFR-TKI were all superior to those of first-generation EGFR-TKI alone， with significant differences （P<0.05）. Meanwhile， the incidence of adverse reaction/events， such as the skin toxic response [RR=0.74，95%CI （0.63， 0.86）]， gastrointestinal reaction [RR=0.54，95%CI （0.41， 0.71）]， damage to hepatic function [RR=0.41， 95%CI （0.26， 0.67）] in Chinese medicine combined with first-generation EGFR-TKI group were lower than those in first-generation EGFR-TKI group， with significant differences （P<0.01）. There was no publication bias according to Begg Rank correlation test. In short， traditional Chinese medicine combined with first-generation EGFR-TKI had a better efficacy and safety in treating advanced NSCLC than EGFR-TKI alone. However， due to the small sample size and the low methodological quality of included papers， the conclusion still needs to be further proved by high-quality， large-sample randomized controlled trials.

[Key words] traditional Chinese medicine；EGFR-TKI；non-small cell lung cancer；system evaluation；Meta-analysis

原发性支气管肺癌（primary bronchogenic carcinoma）是我国最常见的恶性肿瘤之一，也是我国城市人口恶性肿瘤死亡原因的第1位，其中，非小细胞肺癌（non-small cell lung cancer，NSCLC）占肺癌总数的85%。据国家癌症中心2015年发布数据显示，2006—2011年我国肺癌5年患病率是130.2（1/10万）。其中男性84.6（1/10万），居恶性肿瘤第2位；女性45.6（1/10万），居恶性肿瘤第4位[1]。随着我国工业化进程加快，雾霾、废气、粉尘等环境污染不断恶化，原发性肺癌发病率不断攀升，且呈现年轻化趋势，严重危害我国社会经济发展及人民生命健康，高昂的治疗费用使国家、社会及家庭经济不堪重负。

随着个体化基因靶向治疗药物研发的飞速发展，吉非替尼、厄洛替尼、埃克替尼等第一代表皮……