分子靶向药物联合多西他赛和泼尼松治疗转移性去势抵抗性前列腺癌的Meta分析

Efficacy and safety of molecular targeted agents combined with docetaxel plus prednisone for patients with metastatic castration-resistant prostate cancer:A Meta-analysis

目的：系统评价分子靶向药物联合多西他赛和泼尼松治疗转移性去势抵抗性前列腺癌的疗效与安全性。方法：计算机检索Embase、Cochrane Library、PubMed、中国知网、万方数据库、维普中文科技期刊数据库和中国生物医学文献数据库,按照文献纳入标准和排除标准选择应用分子靶向药物联合多西他赛和泼尼松治疗转移性去势抵抗性前列腺癌的相关文献,评价文献质量并提取资料后,应用STATA 12.0软件进行Meta分析。其中,试验组采用分子靶向药物联合多西他赛和泼尼松治疗方案,对照组采用多西他赛联合泼尼松方案治疗。观察终点包括总生存（overall survival,OS）时间、无进展生存（progressionfree survival,PFS）时间、客观缓解率（objective response rate,ORR）、血清前列腺特异性抗原（prostate-specifi c antigen,PSA）水平、3~4级不良反应和致死性不良事件。结果：共纳入5项临床随机对照试验,总样本量为5 886例。Meta分析结果显示,分子靶向药物联合多西他赛和泼尼松组与多西他赛联合泼尼松组相比,中位PFS时间明显延长[风险比为0.93,95%可信区间（confi dence interval,CI）为0.87~0.99,P=0.018],而OS时间[风险比为0.98,95%CI为0.91~1.04,P=0.441]、ORR（比值比为1.317,95%CI为0.94~1.84,P=0.106）和PSA水平（比值比为1.073,95%CI为0.82~1.40,P=0.604）的差异均无统计学意义。在不良反应方面,试验组可使3~4级不良反应（相对危险度为1.187,95%CI为0.99~1.42,P=0.062）和致死性不良事件（相对危险度为1.298,95%CI为1.02~2.22,P=0.039）的发生率增高。结论：分子靶向药物联合多西他赛和泼尼松治疗转移性去势抵抗性前列腺癌可以延长患者的PFS时间,但是分子靶向药物可增加不良反应的发生率,在临床应用时必须加强预防和对症治疗。

Objective：To evaluate the efficacy and safety of docetaxel-prednisone chemotherapy in combination with molecular targeted agents（MTAs） for patients with metastatic castrationresistant prostate cancer（mCRPC）.Methods：A computer-based online search was performed by using Embase,Cochrane Library,PubMed,CNKI（China National Knowledge Infrastructure）,Wanfang database,VIP Chinese Science Technology Journal Database and Chinese Biomedical Literature Database.According to the inclusion and exclusion criteria,the literatures about MTAs in combination with docetaxel plus prednisone for treatment of mCRPC were selected.After evaluating the quality of the included literature and extracting their data,the Meta-analysis was performed using STATA 12.0 software.In this study,the test group was treated with MTAs combined with docetaxel plus prednisone,while the control group was treated with docetaxel plus prednisone.The primary endpoints included overall survival（OS）,progression-free survival（PFS）,objective response rate（ORR）,prostate-specific antigen（PSA）,grades 3-4 adverse reactions and lethal adverse events.Results：Five randomized controlled trials involving 5 886 patients were included.The Metaanalysis showed that PFS was significantly improved in MTAs combined with docetaxel plus prednisone group as compared with docetaxel plus prednisone group [HR（hazard ratio） =0.93,95% confidence interval（CI）：0.87-0.99,P = 0.018],though there were no significant differences in OS（HR = 0.98,95% CI ：0.91-1.04,P = 0.441）,ORR [OR（odds ratio） =1.317,95% CI ：0.94-1.84,P = 0.106] and PSA（OR = 1.073,95% CI ：0.82-1.40,P = 0.604）between the two groups.In terms of adverse reactions,there were higher incidence rates of developing grades 3-4 adverse reactions [RR（relative risk） = 1.187,95% CI ：0.99-1.42,P = 0.062] and lethal adverse events（RR = 1.298,95% CI ：1.02-2.22,P = 0.039） in the test group than those in the control group.Conclusion：MTAs combined with docetaxel plus prednisone in the treatment of patients with mCRPC can prolong the PFS time.Meanwhile,MTAs increase the incidence rates of adverse reactions,which should be prevented and symptomatically treated.