克唑替尼治疗非小细胞肺癌有效性和安全性的系统评价

Effectiveness and safety of crizotinib in the treatment of non-small cell lung cancer:a systematic review

目的系统评价克唑替尼治疗非小细胞肺癌的疗效和安全性。方法计算机检索Cochrane图书馆(2017年第5期)、Pub Med、Embase、中国生物医学文献数据库、中国期刊全文数据库、维普期刊资源整合服务平台和万方数据知识服务平台,检索时限均从建库至2017年5月。纳入克唑替尼治疗非小细胞肺癌的随机对照试验、非随机对照试验以及病例序列和个案报道。由2位研究人员根据纳入与排除标准独立进行文献筛选、数据提取、质量评价并交叉核对结果,然后进行Meta分析或描述性分析。结果共纳入15个研究,包括4个随机对照试验,1个非随机对照试验,4个病例序列,6个个案报道。研究结果显示:克唑替尼组和化学疗法(化疗)组无进展生存期分别为8个月和4.6个月;克唑替尼组反应率高于化疗组,差异有统计学意义[RR=2.35,95%CI(1.59,3.46),P<0.000 1];应用克唑替尼治疗后1年生存率为74.5%~78.6%。不良反应发生率方面,克唑替尼组视觉障碍、味觉障碍、腹泻、呕吐、便秘、转氨酶升高、上呼吸道感染、水肿、头晕的发生率高于常规化疗组,而白细胞减少、血小板减少、脱发及疲劳的发生率低于常规化疗组,差异有统计学意义(P<0.05)。亚组分析结果:克唑替尼用于间变淋巴瘤激酶基因阳性患者无进展生存期为8个月,要长于阴性患者的4个月。结论基于当前证据,克唑替尼用于非小细胞肺癌患者的治疗效果优于化疗。受纳入研究质量限制,上述结论尚需开展更多高质量研究予以验证。

Objective To systematically review the efficacy and safety of crizotinib in the treatment of non-small cell lung cancer （NSCLC）. Method We electronically searched databases including the Cochrane Library （Issue 5,2017）, PubMed, Embase, China Biology Medicine Database, China National Knowledge Internet Database, VIP Database and Wangfang Data from the establishment to May 2017. The randomized controlled trials （RCTs）, non-RCTs, case series and case reports on crizotinib for NSCLC were included. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, assessed the methodological quality of included studies, then make Meta- analysis and descriptive analysis. Result A total of 15 studies were included, including 4 RCTs, 1 non-RCT, 4 case series and 6 case reports. The results indicated that the progression-free survival time of crizotinib group was 8 months, which was better than chemotherapy group （4.6 months）. The results of Meta-analysis showed that the response rate in the crizotinib group was higher than that in the chemotherapy group [RR=2.35, 95%CI （1.59, 3.46）, P〈0.000 1]. The one year survival rate in the crizotinib group was 74.5%-78.6%. The incidences of adverse reactions including dysopsia, dysgeusia, diarrhea, vomiting, constipation, transaminase lifts, upper respiratory tract infection, edema and dizziness in the crizotinib group were higher than those in the chemotherapy group （P〈0.05）, while the incidences of adverse reactions including leukopenia, thrombocytopenia, alopecia and fatigue in crizotinib group were lower than those in the chemotherapy group （P〈0.05）. Subgroup analysis under precision treatment showed the progression-free survival time of anaplastic lymphoma kinase （ALK）-positive group was 8 months, and it was longer than ALK-negative group of 4 months. Conclusions Based on current evidence, crizotinib is better than chemotherapy for NSCLC. Due to limited quality of the included studies, the above conclusion needs to be verifed by more high quality studies.