阿比特龙治疗去势抵抗性前列腺癌疗效和安全性的Meta分析

Efficacy and safety of abiraterone acetate in the treatment of castration-resistant prostate cancer: a meta-analysis

目的系统评价阿比特龙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CNKI、WanFang Data、VIP、Web of Science、PubMed、EMbase和The Cochrane Library数据库,搜集关于阿比特龙治疗去势抵抗性前列腺癌的随机对照试验,检索时限均从建库至2020年12月31日。由2位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果共纳入25个随机对照试验,包括8654例患者。Meta分析结果显示:阿比特龙治疗去势抵抗性前列腺癌在中位影像学无进展生存[MD=5.81,95%CI(3.58,8.03),P<0.01]、PSA反应率[RR=2.77,95%CI(1.65,4.65),P<0.01]、中位总生存[MD=6.44,95%CI(4.54,8.33),P<0.01]、中位PSA进展时间[MD=2.57,95%CI(1.30,3.84),P<0.01]、中位PSA无进展生存[MD=6.74,95%CI(5.08,8.39),P<0.01]、睾酮水平控制[MD=-0.41,95%CI(-0.68,-0.14),P<0.01]、PSA水平控制[MD=-8.06,95%CI(-13.82,-2.31),P<0.01]、有效率[RR=2.94,95%CI(1.89,4.58),P<0.01]、完全缓解人数[RR=1.66,95%CI(1.02,2.72),P<0.05]、粒细胞减少[RR=0.18,95%CI(0.07,0.45),P<0.01]及KPS评分[MD=4.29,95%CI(4.06,4.52),P<0.01]方面明显优于非阿比特龙治疗组。在不良反应方面,阿比特龙组的血压升高[RR=2.04,95%CI(1.62,2.57),P<0.01]、心脏疾病[RR=2.27,95%CI(1.80,2.86),P<0.01]及低血钾[RR=2.89,95%CI(1.59,5.26),P<0.01]发生率明显高于非阿比特龙治疗组;在不良反应导致的停药人数[RR=1.26,95%CI(0.98,1.61),P>0.05]、体液潴留或水肿[RR=1.23,95%CI(0.73,2.09),P>0.05]、肝功能损害[RR=1.66,95%CI(0.93,2.97),P>0.05]、疲劳无力[RR=0.97,95%CI(0.73,1.29),P>0.05]、贫血[RR=0.86,95%CI(0.64,1.16),P>0.05]及血糖升高[RR=1.51,95%CI(0.96,2.36),P>0.05]方面,两组差异均无统计学意义。结论阿比特龙可有效延缓去势抵抗性前列腺癌患者的病情进展,延长生存期,提高患者生活质量。受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证。

Objective To systematically review the efficacy and safety of abiraterone acetate in the treatment of castration-resistant prostate cancer.Methods CNKI,WanFang Data,VIP,Web of Science,PubMed,EMbase and The Cochrane Library databases were electronically searched to collect randomized controlled trials on abiraterone in the treatment of castration-resistant prostate cancer from inception to December 31^(st),2020.Two reviewers independently screened literature,extracted data and evaluated the risk of bias of the included studies.Meta-analysis was then performed using RevMan 5.3 software.Results A total of 25 randomized controlled trials involving 8654 patients were included.Meta-analysis results showed that the median radiographic progression-free survival(MD=5.81,95%CI 3.58 to 8.03,P<0.01),PSA response rate(RR=2.77,95%CI 1.65 to 4.65,P<0.01),median overall survival(MD=6.44,95%CI 4.54 to 8.33,P<0.01),median time to PSA progression(MD=2.57,95%CI 1.30 to 3.84,P<0.01),median PSA progressionfree survival(MD=6.74,95%CI 5.08 to 8.39,P<0.01),testosterone level control(MD=-0.41,95%CI-0.68 to-0.14,P<0.01),PSA level control(MD=-8.06,95%CI-13.82 to-2.31,P<0.01),effective rate(RR=2.94,95%CI 1.89 to 4.58,P<0.01),complete remission(RR=1.66,95%CI 1.02 to 2.72,P<0.05),granulocytopenia(RR=0.18,95%CI 0.07 to 0.45,P<0.01)and KPS score(MD=4.29,95%CI 4.06 to 4.52,P<0.01)were significantly superior to non-abiraterone treatment group.The incidence of hypertension(RR=2.04,95%CI 1.62 to 2.57,P<0.01),heart disease(RR=2.27,95%CI 1.80 to 2.86,P<0.01)and hypokalemia(RR=2.89,95%CI 1.59 to 5.26,P<0.01)adverse reactions were significantly higher than those in non-abiraterone group.The number of drug withdrawals caused by adverse reactions(RR=1.26,95%CI 0.98 to 1.61,P>0.05),fluid retention or edema(RR=1.23,95%CI 0.73 to 2.09,P>0.05),liver function damage(RR=1.66,95%CI 0.93 to 2.97,P>0.05),fatigue and weakness(RR=0.97,95%CI 0.73 to 1.29,P>0.05),anemia(RR=0.86,95%CI 0.64 to 1.16,P>0.05)and elevated blood glucose(RR=1.51,95%CI 0.96 to 2.36,P>0.05),were not significantly different between the two groups.Conclusion Abiraterone acetate can effectively delay the progression of castration-resistant prostate cancer,prolong the survival period,and improve the quality of life.Due to the limited quantity and quality of the included studies,more high-quality studies are needed to verify the above conclusion.