中药注射剂联合化疗治疗中晚期食管癌有效性与安全性的网状Meta分析

Effectiveness and safety of traditional Chinese medicine injections combined with chemotherapy in treatment of middle and advanced esophageal cancer:A network Meta-analysis

目的基于网状Meta分析方法比较中药注射剂联合常规化疗治疗中晚期食管癌的疗效和安全性。方法计算机检索中国知网、万方、维普、中国生物医学文献数据库、PubMed、Cochrane Library、Embase、Web of Science 8大数据库自建库至2022年7月31日所收录的中药注射剂联合常规化疗治疗中晚期食管癌的随机对照试验。2人独立对文献进行筛选、提取数据和质量评价。采用R软件4.0.3、Stata 14软件分析数据。结果共纳入51项研究,涉及3865例中晚期食管癌患者,试验组干预措施为艾迪注射液(Aidi Injection,AD)、复方苦参注射液(Fufang Kushen Injection,FFKS)、康莱特注射液(Kanglaite Injection,KLT)、消癌平注射液(Xiaoaiping Injection,XAP)分别联合常规化疗,对照组为常规化疗。网状Meta分析结果显示联合常规化疗:(1)在提高食管癌客观缓解率(objective response rate,ORR)方面,中药注射剂的排名为FFKS(SUCRA=97.4%)>AD(SUCRA=58.0%)>XAP(SUCRA=57.3%)>KLT(SUCRA=36.4%);(2)在提高疾病控制率(disease control rate,DCR)方面,中药注射剂的排名为FFKS(SUCRA=96.0%)>AD(SUCRA=76.3%)>XAP(SUCRA=40.3%)>KLT(SUCRA=33.9%);(3)在改善食管癌患者生活质量(quality of life,QOL)方面,中药注射剂的排名为XAP(SUCRA=71.3%)>FFKS(SUCRA=69.9%)>KLT(SUCRA=68.6%)>AD(SUCRA=40.1%);(4)在改善食管癌患者化疗后白细胞计数(white blood cell count,WBC)下降方面,中药注射剂的排名为KLT(SUCRA=87.3%)>XAP(SUCRA=62.2%)>FFKS(SUCRA=61.0%)>AD(SUCRA=39.3%);(5)在改善免疫功能方面,AD、KLT可以显著改善化疗后CD4^(+)水平,且在改善化疗后CD3^(+)与CD4^(+)/CD8^(+)水平方面,AD的疗效优于FFKS,差异皆有统计学意义(P<0.05);(6)在不良反应发生情况方面,4种中药注射液联合常规化疗的不良反应发生率明显低于单纯化疗且差异具有统计学意义(P<0.05)。结论现有证据表明,在常规化疗的基础上联合4种中药注射剂均可提高中晚期食管癌患者的QOL,降低因化疗引起的不良反应。其中,在提高ORR和DCR方面FFKS效果最佳,XAP改善化疗后患者的QOL效果最好,在化疗后改善WBC下降方面KLT最佳,但由于纳入研究数量和质量的限制,结论仍需高质量的研究加以验证。

Objective To compare the efficacy and safety of traditional Chinese medicine injections combined with conventional chemotherapy in the treatment of middle and advanced esophageal cancer based on network Meta-analysis.Methods The randomized controlled trials(RCTs)of traditional Chinese medicine(TCM)injections combined with conventional chemotherapy in treatment of middle and advanced esophageal cancer were searched in CNKI,Wanfang,VIP,SinoMed,PubMed,Cochrane Library,Embase and Web of Science database from inception to July 31,2022.Literature screening,data extraction,the quality assessment was independently conducted by two authors.R 4.0.3 and Stata 14 were used for data analysis.Results A total of 51 RCTs were eventually included,involving 3865 patients.The intervention measures in the experiment group were Aidi Injection(艾迪注射液,AD),Fufang Kushen Injection(复方苦参注射液,FFKS),Kanglaite Injection(康莱特注射液,KLT),Xiaoaiping Injection(消癌平注射液,XAP)respectively combined with conventional chemotherapy and the control group was conventional chemotherapy.The results of network Meta-analysis showed that,combined with chemotherapy:①In terms of improving the objective response rate(ORR),the order of efficacy was FFKS(SUCRA=97.4%)>AD(SUCRA=58.0%)>XAP(SUCRA=57.3%)>KLT(SUCRA=36.4%);②In terms of improving the disease control rate(DCR),the order of efficacy was FFKS(SUCRA=96.0%)>AD(SUCRA=76.3%)>XAP(SUCRA=40.3%)>KLT(SUCRA=33.9%);③In terms of improving the quality of life(QOL),the order of efficacy was XAP(SUCRA=71.3%)>FFKS(SUCRA=69.9%)>KLT(SUCRA=68.6%)>AD(SUCRA=40.1%);④In terms of improving the white blood cell count(WBC)of patients with esophageal cancer after chemotherapy,the order of efficacy was KLT(SUCRA=87.3%)>XAP(SUCRA=62.2%)>FFKS(SUCRA=61.0%)>AD(SUCRA=39.3%);⑤In terms of improving immune function,AD and KLT could significantly improve the level of CD4^(+)after chemotherapy,and in terms of improving CD3^(+)and CD4^(+)/CD8^(+)after chemotherapy,the efficacy of AD was better than that of FFKS,and the differences were statistically significant(P<0.05);⑥In terms of the overall incidence of adverse reactions,the incidence of adverse reactions of four kinds of TCM injections combined with conventional chemotherapy was significantly lower than that of chemotherapy alone,and the difference was statistically significant(P<0.05).Conclusion The existing evidence showed that the combination of TCM injections with conventional chemotherapy could improve the QOL of patients with middle and advanced esophageal cancer and reduce adverse reactions caused by chemotherapy.FFKS has the best effect in improving ORR and DCR;XAP has the best effect in improving QOL of patients after chemotherapy,and KLT has the best effect in improving the decline of WBC after chemotherapy.However,due to the limitation of the number and quality of studies included,the conclusion still needs to be verified by high-quality studies.