PARP抑制剂致血液系统不良反应的Meta分析

Meta-analysis of Adverse Drug Reaction of Hematological System by PARP Inhibitors

目的:系统评价聚腺苷二磷酸聚合酶(PARP)抑制剂在血液系统方面的安全性,为临床合理用药提供循证依据。方法:计算机检索PubMed、Embase、Cochrane图书馆、ScienceDirect、中国期刊全文数据库、中国生物医学文献数据库、中国科技期刊全文数据库、万方数字化期刊全文数据库,检索时限为2014年5月至2019年6月。收集单用PARP抑制剂或PARP抑制剂联合化学治疗药物(试验组)对比单用化学治疗药物或安慰剂或化学治疗药物联合安慰剂(对照组)的随机对照试验(RCT)。筛选文献、提取资料并采用Cochrane系统评价员手册5.1.0推荐的偏倚风险评估工具对纳入文献质量进行评价后,采用Rev Man 5.3软件进行Meta分析,同时进行敏感性分析和发表偏倚分析。结果:共纳入10项RCT,共计3129例患者。Meta分析结果显示,试验组患者贫血≥3级发生率[RR=7.27,95%CI(2.74,19.27),P<0.0001]、中性粒细胞减少≥3级发生率[RR=2.46,95%CI(1.43,4.24),P=0.001]、白细胞减少≥3级发生率[RR=1.71,95%CI(1.15,2.54),P=0.008]均显著高于对照组;两组患者血小板减少≥3级发生率比较,差异无统计学意义[RR=3.54,95%CI(0.66,19.05),P=0.14]。亚组分析结果显示,单用PARP抑制剂和联用PARP抑制剂、化学治疗药物患者的贫血≥3级发生率,中性粒细胞减少≥3级发生率以及联用PARP抑制剂、化学治疗药物患者的白细胞减少≥3级发生率均显著高于单用安慰剂组、单用化学治疗药物或化学治疗药物联合安慰剂者(P<0.05)。敏感性分析支持上述结果,但存在发表偏倚的可能性较大。结论:PARP抑制剂治疗癌症可致患者发生血液系统不良反应,主要表现为贫血、中性粒细胞减少和白细胞减少。应谨慎解读上述结果。

OBJECTIVE:To evaluate the safety of PARP inhibitors in hematological system,and to provide evidence-based evidence for rational drug use in the clinic.METHODS:Retrieved from PubMed,Embase,Cochrane Library,ScienceDirect,CNKI,CBM,VIP and Wanfang data from May 2014 to June 2019,randomized controlled trials(RCTs)about PARP inhibitors or PARP inhibitors combined with chemical treatment drugs(trial group)versus chemical treatment drugs alone,placebo alone or chemical treatment drugs combined with placebo(control group)were collected.After literature screening,data extraction and quality evaluation with bias risk assessment tool recommended by Cochrane systematic evaluator manual 5.1.0,and Meta-analysis was performed by using Rev Man 5.3 software,and sensitivity analysis and publication bias analysis.RESULTS:A total of 10 RCTs were included,involving 3129 patients.Meta-analysis showed that the incidence of anemia≥grade 3[RR=7.27,95%CI(2.74,19.27),P<0.0001],neutropenia≥grade 3[RR=2.46,95%CI(1.43,4.24),P=0.001],and leukopenia≥grade 3 in trial group[RR=1.71,95%CI(1.15,2.54),P=0.008]in trial group were significantly higher than control group.There was no statistically significant difference in the incidence of thrombocytopenia≥grade 3 between two groups[RR=3.54,95%CI(0.66,19.05),P=0.14].Results of sub-group analysis showed that the incidence of anemia≥grade 3 and neutropenia≥grade 3 in the patients receiving PARP inhibitors alone,PARP inhibitors combined with chemical treatment drugs as well as the incidence of leukopenia≥grade 3 in the patients receiving PARP inhibitors combined with chemical treatment drugs were significantly higher than those receiving placebo alone,chemical treatment drugs alone or chemical treatment drugs combined with placebo(P<0.05).Sensitivity analysis supported the above results;howerer,publication bias was possibility.CONCLUSIONS:PARP inhibitor in the treatment of cancer can cause hematological system adverse drug reaction,mainly manifesting as anemia,neutropenia and leukopenia.These results should be interpreted with caution.