多西他赛单药或联合血管内皮生长因子抑制剂治疗去势抵抗性前列腺癌疗效和安全性的Meta分析

Docetaxel-based therapy with or without inhibitor of VEGF agents as first-line chemotherapy for castration-resistant prostate cancer:a Meta-analysis of four randomized controlled trials

目的系统评价多西他赛联合血管内皮生长因子抑制剂治疗去势抵抗性前列腺癌的疗效和安全性。方法计算机检索EMbase、PubMed、Cochran,查找多西他赛单独与联合血管内皮生长因子抑制剂(inhibition of VEGF Agents)比较治疗前列腺癌的随机对照试验(RCT),检索时限均从建库至2014年9月1日。按照纳入/排除标准对纳入研究进行资料提取、方法学质量评价后,采用RevMan 5.2软件进行Meta分析,并采用Jadad评分进行文献质量评估。结果共纳入4个RCT,2 386例患者。Meta分析结果显示,多西他赛联合血管内皮生长因子抑制剂治疗组与多西他赛单药组比较,前列腺特异性抗原(PSA)反应率[RR=0.94,95%CI(0.77,1.15),P=0.56],客观反应率[RR=0.91,95%CI(0.46,1.80),P=0.79],在中位总生存时间方面[HR=0.94,95%CI(0.85,1.04),P=0.23],和无疾病进展时间[HR=1.13,95%CI(0.53,2.38),P=0.76],两组差异无统计学意义;但治疗相关病死率[RR=2.70,95%CI(1.51,4.85),P=0.0009]联合组高于单药组,血栓发生率[RR=0.55,95%CI(0.39,0.78),P=0.0008],联合组低于单药组。结论目前有限证据显示多西他赛联合血管内皮生长因子抑制剂用于治疗去势抵抗性前列腺癌患者方面,并不能提高患者中位总生存和无疾病进展时间,且可能增加治疗相关病死率。上述结论尚需更多高质量大样本RCT加以验证。

Objective To assess the efficacy and safety of docetaxel-based chemotherapy combined with inhibitor of VEGF agents（combined therapy）and docetaxel-based chemotherapy without inhibitor of VEGF agents（single therapy）for the treatment of castration-resistant prostate cancer.Methods Data bases such as EMbase,PubMed,and Cochrane were searched to retrieve randomized controlled trials（RCT）which compared docetaxel-based therapy with or without inhibitor of VEGF in the treatment of prostate cancer.The searching time limit was from the establishment of the database to Sept.1st,2014.After data were extracted and evaluated,Meta-analysis was conducted with RevMan5.2,and quality of literature was evaluated with jadad method.Results A total of 4 RTCs involving 2 386 patients were included.Meta-analysis showed,prostate-specific antigen（PSA）response rate was[RR=0.94,95%CI（0.77,1.15）,P=0.56],objective response rate was[RR=0.91,95%CI（0.46,1.80）,P=0.79],overall survival（OS）[HR=0.94,95%CI（0.85,1.04）,P=0.23],progression-free survival time（PFS）was[HR=1.13,95%CI（0.53,2.38）,P=0.76],and there was no statistical difference between the two types of treatment.The combined therapy had higher treating-related mortality[RR=2.70,95%CI（1.51,4.85）,P=0.000 9],while single therapy has higher incidence of thrombus[RR=0.55,95%CI（0.39,0.78）,P=0.000 8].Conclusions When docetaxel with inhibitor of VEGF agents is used to treat castration-resistant prostate cancer,it may not increase patients＇overall survival time and progression-free survival time,whereas may increase the related mortality in treating progress.Further RCTs with big samples should be conducted to verify the results.