参芪扶正注射液联合常规化疗对晚期非小细胞肺癌患者免疫功能影响的Meta分析

Meta-analysis of the Effects of Shenqi Fuzheng Injection Combined with Conventional Chemotherapy on the Immune Function of Patients with Advanced NSCLC

目的:系统评价参芪扶正注射液联合常规化疗对晚期非小细胞肺癌(NSCLC)患者免疫功能的影响,旨在为临床用药提供循证参考。方法:计算机检索Cochrane图书馆、PubMed、Medline、Embase、中国知网、万方数据库、维普数据库、中国生物医学文献数据库,收集参芪扶正注射液联合常规化疗(试验组)对比常规化疗(对照组)用于晚期NSCLC的随机对照试验(RCT)。筛选文献、提取资料并采用Cochrane系统评价员手册5.1.0偏倚风险评估工具对纳入文献质量进行评价后,采用Rev Man 5.3软件进行Meta分析。结果:共纳入16篇文献,共计1324例患者。Meta分析结果显示,两组患者客观缓解率[RR=1.14,95%CI(0.91,1.43),P=0.25]、CD8^+水平[MD=-1.26,95%CI(-4.10,1.59),P=0.39]比较,差异均无统计学意义。试验组患者CD3^+水平[MD=17.48,95%CI(13.40,21.56),P<0.00001]、CD4^+水平[MD=12.26,95%CI(8.39,16.13),P<0.00001]、CD4^+/CD8^+[MD=0.33,95%CI(0.27,0.39),P<0.00001]、自然杀伤细胞百分比[MD=9.33,95%CI(5.72,12.94),P<0.00001]均显著高于对照组。按参芪扶正注射液用药天数进行的亚组分析结果显示,使用参芪扶正注射液7~14 d试验组患者的CD3^+水平[MD=17.11,95%CI(12.37,23.17),P<0.00001]、CD4^+水平[MD=13.28,95%CI(8.33,18.23),P<0.00001]、CD4^+/CD8^+水平[MD=0.36,95%CI(0.28,0.43),P<0.00001]、自然杀伤细胞百分比[MD=12.06,95%CI(7.52,16.61),P<0.0001]均显著高于对照组;使用参芪扶正注射液21 d的CD3^+水平[MD=14.88,95%CI(7.51,22.26),P<0.00001]、CD4^+水平[MD=10.56,95%CI(5.57,15.56),P<0.00001]、CD8^+水平[MD=3.02,95%CI(1.80,4.23),P<0.00001]、CD4^+/CD8^+[MD=0.29,95%CI(0.23,0.35),P<0.00001]、自然杀伤细胞百分比[MD=5.58,95%CI(2.49,8.67),P=0.0004]均显著高于对照组;使用参芪扶正注射液7~14 d试验组患者的CD8+水平较对照组的差异无统计学意义[MD=-4.26,95%CI(-12.60,4.09),P=0.32]。试验组患者白细胞减少、恶心呕吐、肾功能损伤发生率均显著低于对照组(P<0.05),而两组患者血红蛋白减少、血小板减少发生率比较差异均无统计学意义(P>0.05)。发表偏倚结果显示,本研究存在发表偏倚的可能有性较大。结论:参芪扶正注射液联合常规化疗可能会改善晚期NSCLC患者的免疫功能并提高安全性,但此结论尚有待更多大样本、多中心、高质量的RCT进一步验证。

OBJECTIVE:To systematically evaluate the effects of Shenqi fuzheng injection combined with conventional chemotherapy on the immune function of patients with advanced non-small cell lung cancer(NSCLC),and provide evidence-based reference for clinical medication.METHODS:Retrieved from Cochrane Library,PubMed,Medline,Embase,CNKI,Wanfang database,VIP and CBM,Shenqi fuzheng injection combined with conventional chemotherapy(trial group)versus conventional therapy(control group)for advanced NSCLC were collected.After literature screening,data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0 risk evaluation tool,Meta-analysis was performed by using Rev Man 5.3 statistical software.RESULTS:A total of 16 literatures were included,involving 1324 cases.Results of Meta-analysis showed that there were no statistical significance in the difference of objective remission rate(ORR)[RR=1.14,95%CI(0.91,1.43),P=0.25]and the level of CD8^+[MD=-1.26,95%CI(-4.10,1.59),P=0.39]between 2 groups.The levels of CD3^+[MD=17.48,95%CI(13.40,21.56),P<0.00001],CD4^+[MD=12.26,95%CI(8.3916.13),P<0.00001],CD4^+/CD8^+[MD=0.33,95%CI(0.27,0.39),P<0.00001]and the percentage of NK cells[MD=9.33,95%CI(5.72,12.94),P<0.00001]in trial group were significantly higher than control group.Results of subgroup analysis for medication duration of Shenqi fuzheng injection showed that after 1-14 d treatment of Shenqi fuzheng injection,the levels of CD3^+[MD=17.11,95%CI(12.37,23.17),P<0.00001],CD4^+[MD=13.28,95%CI(8.33,18.23),P<0.00001],CD4^+/CD8^+[MD=0.36,95%CI(0.28,0.43),P<0.00001]and the percentage of NK cells[MD=12.06,95%CI(7.52,16.61),P<0.0001]in trial group were significantly higher than control group.After 21 d treatment of Shenqi fuzheng injection,the levels of CD3^+[MD=14.88,95%CI(7.51,22.26),P<0.00001],CD4^+[MD=10.56,95%CI(5.57,15.56),P<0.00001],CD8^+[MD=3.02,95%CI(1.80,4.23),P<0.00001],CD4^+/CD8^+[MD=0.29,95%CI(0.23,0.35),P<0.00001]and the percentage of NK cells[MD=5.58,95%CI(2.49,8.67),P=0.0004]in trial group were significantly higher than control group.There was no statistical significance in the level of CD8^+ between 2 groups after 7-14 d treatment of Shenqi fuzheng injection[MD=-4.26,95%CI(-12.60,4.09),P=0.32].The incidence of leukopenia,nausea and vomiting,and renal dysfunction in trial group were significantly lower than control group.There was no statistical significance in the incidence of hemoglobin decreased and thrombocytopenia between 2 groups.The results of publication bias showed that there was a greater possibility of publication bias in this study.CONCLUSIONS:Shenqi fuzheng injection combined with conventional chemotherapy may improve the immune function of patients with advanced NSCLC and improve the safety after chemotherapy.But more large-scale,milltiple-center and high-quality RCT are needed to validate this conclusion.