贝伐单抗不同给药方式治疗恶性胸腔积液有效性和安全性的Meta分析
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篇名: 贝伐单抗不同给药方式治疗恶性胸腔积液有效性和安全性的Meta分析
TITLE: Meta-analysis of the Efficacy and Safety of Different Administration Routes of Bevacizumab in the Treatment of Malignant Pleural Effusion
摘要: 目的:系统评价贝伐单抗不同给药方式治疗恶性胸腔积液的有效性和安全性,为临床合理用药提供循证参考。方法:计算机检索Cochrane图书馆、PubMed、Embase、维普电子期刊全文数据库、中国学术文献出版总库、万方数据库和中国生物医学文献数据库,收集不同给药方式下贝伐单抗联合或不联合化疗药物(试验组)对比化疗药物(对照组)治疗恶性胸腔积液的临床研究。筛选文献并提取资料,采用Cochrane系统评价员手册5.3推荐的偏倚风险评估工具评价随机对照试验(RCT)文献质量,采用纽卡斯尔-渥太华量表评价回顾性研究文献质量。采用RevMan5.3软件进行Meta分析,采用Stata13.0软件进行网状Meta分析,采用R3.6.1软件进行干预措施排序。结果:共纳入29项研究,其中21项为RCT、8项为回顾性研究,共计2254例患者。涉及贝伐单抗+化疗药物(胸腔灌注)、贝伐单抗+化疗药物(静脉滴注)、贝伐单抗(胸腔灌注)、化疗药物(胸腔灌注)、化疗药物(静脉滴注)等5种干预措施。网状Meta分析结果显示,贝伐单抗+化疗药物(胸腔灌注)与贝伐单抗+化疗药物(静脉滴注)[OR=0.81,95%CI(0.13,4.60),P>0.05]、化疗药物(胸腔灌注)与化疗药物(静脉滴注)[OR=0.47,95%CI(0.07,3.10),P>0.05]、贝伐单抗+化疗药物(静脉滴注)与化疗药物(静脉滴注)[OR=0.56,95%CI(0.27,1.20),P>0.05]的总有效率比较,差异均无统计学意义;贝伐单抗+化疗药物(胸腔灌注)[OR=3.10,95%CI(2.10,4.50),P<0.05]、贝伐单抗(胸腔灌注)[OR=1.90,95%CI(0.99,3.90),P<0.05]的总有效率均显著高于化疗药物(胸腔灌注)。网状Meta排序为贝伐单抗+化疗药物(静脉滴注)>贝伐单抗+化疗药物(胸腔灌注)>贝伐单抗(胸腔灌注)>化疗药物(静脉滴注)>化疗药物(胸腔灌注)。试验组患者血压升高发生率[RR=2.64,95%CI(1.56,4.43),P=0.0003]、蛋白尿发生率[RR=3.24,95%CI(1.79,5.86),P=0.0001]均显著高于对照组;两组患者粒细胞减少发生率[RR=0.94,95%CI(0.81,1.09),P=0.41]、恶心呕吐发生率[RR=0.87,95%CI(0.73,1.03),P=0.10]比较,差异均无统计学意义。与单独化疗相比,贝伐单抗联合化疗不能延长患者总生存期,但可改善无进展生存期。结论:虽然贝伐单抗联合化疗可显著提高恶性胸腔积液患者的疗效,但胸腔灌注给药方式可增加蛋白尿、血压升高的发生风险。
ABSTRACT: OBJECTIVE:To evaluate the efficacy and s afety of different administration routes of bevacizumab in the treatment of malignant pleural effusion (MPE),and to provide evidence-based reference for rational use of drugs in clinic. METHODS : Retrieved from Cochrane L ibrary,PubMed,Embase,VIP,CNKI,Wanfang database and CBM ,clinical studies were collected , about bevacizumab combined with or without chemotherap eutic drugs (trial group )versus chemotherap eutic drugs (control group ) in the treatment of MPE under different administration routes. After literature screening and data extraction ,the quality of RCTs was evaluated by using bias risk evaluation tool recommended by Cochrane Systematic Evaluator Manual 5.3. Newcastle-Ottawa scale was used to evaluate the quality of the retrospective study. Meta-analysis was performed by using Rev Man 5.3 software, network Meta-analysis was performed by using Stata 13.0 software and intervention measures were ranked by using R 3.6.1 software. RESULTS :A total of 29 studies were included ,involving 21 RCTs and 8 retrospective studies ,including 2 254 patients. The studies involved 5 intervention measures ,such as bevacizumab+chemotherap eutic drugs (thoracic perfusion ),bevacizumab+ chemotherapeutic drugs (ivgtt),bevacizumab(thoracic perfusion ),chemotherapeutic drugs (thoracic perfusion ),chemotherapeutic drugs(ivgtt). Network Meta-analysis showed there was no statistical significance in bevacizumab+chemotherap eutic drugs (thoracic perfusion)and bevacizumab+chemotherap eutic drugs (ivgtt)[OR=0.81,95%CI(0.13,4.60),P>0.05],chemotherapeutic drugs (thoracic perfusion )and chemo therapeutic drugs (ivgtt)[OR= 0.47, 95% CI (0.07,3.10), P>0.05], bevacizumab + Z19SCHX202) chemotherapeutic drugs (ivgtt) and chemotherap eutic drugs (ivgtt) [OR=0.56,95% CI(0.27,1.20),P>0.05]. Total 、 response rate of bevacizumab + chemotherap eutic drugs (thoracic perfusion ) [OR=3.10,95% CI(2.10,4.50),P< 0.05],bevacizumab(thoracic perfusion )[OR=1.90,95%CI (0.99,3.90),P<0.05] were significantly higher than chemotherapeutic drugs (thoracic perfusion ). Network Meta-analysis ranking showed that bevacizumab + chemotherapeutic drugs (ivgtt)> bevacizumab + chemotherapeutic drugs (thoracic perfusion )> bevacizumab(thoracic perfusion )>chemotherapeutic drugs (ivgtt)>chemotherapeutic drugs (thoracic perfusion ). The incidence of elevated blood pressure [RR= 2.64,95%CI(1.56,4.43),P=0.000 3] and proteinuria [RR =3.24,95%CI(1.79,5.86),P=0.000 1] in trial group were significantly higher than control group. There was no statistical significance in the incidence of granulo- cytopenia [RR =0.94,95%CI(0.81,1.09),P=0.41] or nausea and vomiting [RR =0.87,95%CI(0.73,1.03),P=0.10] between 2 groups. Compared with chemotherapy alone ,bevacizumab combined chemotherapy could not prolong the total survival time of patients,but can improve the progression-free survival time. CONCLUSIONS :Bevacizumab combined with chemotherapy can improve the efficacy of MPE patients ,but thoracic perfusion can increase the risk of proteinuria and elevated blood pressure.
期刊: 2020年第31卷第06期
作者: 戴冰,占美,徐珽
AUTHORS: DAI Bing,ZHAN Mei,XU Ting
关键字: 贝伐单抗;不同给药方式;恶性胸腔积液;Meta分析;有效性;安全性
KEYWORDS: Bevacizumab;Different administration routes ;Malignant pleural effusion ;Meta-analysis;Efficacy;Safety
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