新型抗Her-2药物曲妥珠单抗共轭复合物治疗乳腺癌安全性的系统评价  

Systematic review on the safety of the new type Her-2 positive targeted drugs T-DM1 in breast cancer

作　　者：郭子寒 焦园园[1] 范丽萍[1,2] 张艳华[1] 

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所药剂科恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142 [2]北京大学医学部临床药学与药事管理系,北京100191

出　　处：《中国药物应用与监测》2015年第6期339-342,共4页Chinese Journal of Drug Application and Monitoring

基　　金：北京药学会2014年临床药学研究项目:肿瘤患者紫杉醇三周方案给药后关键药代动力学参数Tc>0.05与临床毒性相关性研究

摘　　要：目的:系统评价曲妥珠单抗共轭复合物(ado-trastuzumab emtansine,T-DM1)不良反应的发生率。方法:检索Pub Med、Clinicaltrials.gov和CNKI数据库,收集2015年2月前发表的T-DM1临床研究,采用Rev Man 5.3软件分析。结果:共纳入3项随机对照试验,共计1700例患者。Meta分析结果显示,所有程度不良反应发生率:T-DM1组血小板减少的发生率高于对照组[RR=6.76,95%CI(3.47,13.17),P=0.12,I^2=53%];T-DM1组AST升高的发生率高于对照组[RR=2.68,95%CI(1.40,5.14),P=0.04,I^2=69%];T-DM1组中性粒细胞减少的发生率低于对照组[RR=0.35,95%CI(0.18,0.71),P=0.003,I^2=83%];T-DM1组腹泻的发生率低于对照组[RR=0.34,95%CI(0.25,0.47),P=0.12,I^2=52%];两组贫血的发生率差异无统计学意义[RR=0.87,95%CI(0.51,1.49),P=0.05,I^2=66%]。3-4度不良反应发生率:T-DM1组中性粒细胞减少的发生率低于对照组[RR=0.20,95%CI(0.08,0.50),P=0.02,I^2=75%];T-DM1组腹泻的发生率低于对照组[RR=0.10,95%CI(0.05,0.18),P=0.53,I^2=0%];两组血小板减少的发生率差异无统计学意义[RR=6.93,95%CI(0.80,59.80),P=0.004,I^2=82%];两组贫血的发生率差异无统计学意义[RR=1.21,95%CI(0.65,2.26),P=0.59,I^2=0%];两组AST升高的发生率差异无统计学意义[RR=3.13,95%CI(0.77,12.70),P=0.07,I^2=63%]。结论:与传统化疗方案相比,T-DM1具有良好的安全性。Objective： To systematically evaluate the incidence of adverse reactions about ado-trastuzumab emtansine（T-DM1）. Methods： We searched medical literature from the Pub Med, Clinicaltrials.gov and CNKI. Our meta-analysis included clinical trials published before February 2015. All statistical analyses were performed by Rev Man 5.3 software. Results： A total of 3 randomized controlled trials involving 1700 patients were included. The results of meta-analysis showed that in all-grade adverse reactions, when compared with control group, the incidence of thrombocytopenia was higher in T-DM1 group [RR = 6.76, 95%CI（3.47, 13.17）, P = 0.12, I^2 = 53%]; the incidence of increase of AST was higher in T-DM1 group [RR = 2.68, 95%CI（1.40, 5.14）, P = 0.04, I^2 = 69%]; the incidence of neutropenia was lower in T-DM1 group [RR = 0.35, 95%CI（0.18, 0.71）, P = 0.003, I^2 = 83%]; the incidence of diarrhea was lower in T-DM1 group [RR = 0.34, 95%CI（0.25, 0.47）, P = 0.12, I^2 = 52%]; while, no signifi cant difference was found in anaemia between the two groups [RR = 0.87, 95%CI（0.51, 1.49）, P = 0.05, I^2 = 66%]. When compared with the 3-4 grade adverse reactions of control group, the incidence of neutropenia was lower in T-DM1 group [RR = 0.20, 95%CI（0.08, 0.50）, P = 0.02, I^2 = 75%]; the incidence of diarrhea was lower in T-DM1 group [RR = 0.10, 95%CI（0.05, 0.18）, P = 0.53, I^2 = 0%]; however, no signifi cant difference was found between the two groups in thrombocytopenia [RR = 6.93, 95%CI（0.80, 59.80）, P = 0.004, I^2 = 82%], anaemia [RR = 1.21, 95%CI（0.65, 2.26）, P = 0.59, I^2 = 0%] and increase of AST [RR = 3.13, 95%CI（0.77, 12.70）, P = 0.07, I^2 = 63%]. Conclusion： T-DM1 has a good safety compared to the traditional chemotherapy.

关 键 词：曲妥珠单抗共轭复合物 HER-2阳性 转移性乳腺癌 安全性 Meta分析 系统评价 

分 类 号：R737.9[医药卫生—肿瘤]