Engineering Research Center for Pharmaceuticals and Equipment of Sichuan Province, Chengdu University, Chengdu, China.
College of Pharmacy, Southwest Minzu University, Chengdu, China.
J Clin Pharm Ther. 2021 Apr;46(2):241-255. doi: 10.1111/jcpt.13300. Epub 2020 Nov 2.
PARP inhibitors are currently one of the most promising PARP targeted drugs for patients with certain types of cancer. Gastrointestinal (GI) events are common adverse events for all PARP inhibitors. We conducted this meta-analysis of randomized controlled trials (RCTs) to fully investigate the incidence and the relative risk of GI events in cancer patients receiving PARP inhibitors.
Randomized controlled trials in cancer patients treated with PARP inhibitors were retrieved, and the systematic evaluation was conducted. Embase and PubMed/Medline were searched for articles published till July 2020.
Twenty-nine RCTs and 9529 patients were included. The present meta-analysis suggests that the use of PARP inhibitors significantly increases the risk of developing all-grade nausea (RR, 1.46; 95% CI, 1.29-1.66; p < .00001), vomiting (RR, 1.39; 95% CI, 1.17-1.64; p = .0001), diarrhoea (RR, 1.14; 95% CI, 1.06-1.23; p = .0003) and decreased appetite (RR, 1.24; 95% CI, 1.14-1.36; p < .00001), but not for constipation. And the use of these agents significantly increased the risk of high-grade nausea (RR, 1.99; 95% CI, 1.44-2.74; p < .0001), vomiting (RR, 1.54; 95% CI, 1.11-2.14; p = .01) and decreased appetite (RR, 2.03; 95% CI, 1.22-3.40; p = .007), except for diarrhoea and constipation. Nausea was the most common GI event for these agents. Patients receiving veliparib were associated with a relatively lower risk of all-grade nausea and vomiting. Patients with ovarian cancer tend to have a higher risk of all-grade nausea and vomiting than those with non-ovarian cancer. The risk of all-grade nausea and vomiting tended to be higher when PARP inhibitors treatment was longer.
PARP inhibitors were associated with a significant increased risk of GI events. Clinicians should be aware of these risks and perform regular monitoring.
聚腺苷二磷酸核糖聚合酶（PARP）抑制剂是目前针对某些类型癌症患者最有前途的 PARP 靶向药物之一。胃肠道（GI）事件是所有 PARP 抑制剂的常见不良事件。我们进行了这项随机对照试验（RCT）的荟萃分析，以充分研究接受 PARP 抑制剂治疗的癌症患者中 GI 事件的发生率和相对风险。
检索了接受 PARP 抑制剂治疗的癌症患者的随机对照试验，并进行了系统评价。检索了 Embase 和 PubMed/Medline 数据库，以获取截至 2020 年 7 月发表的文章。
共纳入 29 项 RCT 和 9529 名患者。本荟萃分析表明，PARP 抑制剂的使用显著增加了所有级别恶心（RR，1.46；95%CI，1.29-1.66；p<0.00001）、呕吐（RR，1.39；95%CI，1.17-1.64；p=0.0001）、腹泻（RR，1.14；95%CI，1.06-1.23；p=0.0003）和食欲下降（RR，1.24；95%CI，1.14-1.36；p<0.00001）的风险，但不增加便秘的风险。这些药物的使用显著增加了高级别恶心（RR，1.99；95%CI，1.44-2.74；p<0.0001）、呕吐（RR，1.54；95%CI，1.11-2.14；p=0.01）和食欲下降（RR，2.03；95%CI，1.22-3.40；p=0.007）的风险，除腹泻和便秘外。恶心是这些药物最常见的胃肠道事件。接受 veliparib 治疗的患者发生所有级别恶心和呕吐的风险相对较低。与非卵巢癌患者相比，卵巢癌患者发生所有级别恶心和呕吐的风险更高。PARP 抑制剂治疗时间越长，发生所有级别恶心和呕吐的风险越高。
PARP 抑制剂与 GI 事件的发生风险显著增加相关。临床医生应注意这些风险并进行定期监测。
