6种止吐用药方案预防高致吐风险化疗引起恶心呕吐临床效果的网状meta分析

Network Meta-analysis of the Clinical Efficacy of Six Kinds of Antiemetic Regimens in the Prevention of Nausea and Vomiting Caused by Highly Emetogenic Chemotherapy

关键词:  化疗所致恶心呕吐  高致吐风险化疗  疗效  网状meta分析

Key words:  chemotherapy-induced nausea and vomiting  highly emetogenic chemotherapy  therapeutic efficacy  network meta-analysis

摘要:

目的 采用网状meta分析评价6种止吐用药方案预防高致吐风险化疗（highly emetogenic chemotherapy，HEC）引起的恶心呕吐的疗效。方法 计算机检索中国知网、万方数据、维普医药、PubMed、Embase和Cochrane Library（2019年第8期），检索时限至2019年9月1日，收集5-羟色胺3受体抑制剂[包括第1代5-HT₃和第2代5-HT₃帕洛诺司琼（palonosetron，PAL）]+地塞米松（dexamethasone，DEX）、神经激肽1受体抑制剂（NK-1 receptor antagonist，NK-1RA）+5-HT₃+DEX、奥氮平（olanzapine，OLZ）+5-HT₃+DEX、NEPA（奈妥吡坦300 mg+PAL 0.50 mg）+DEX预防化疗所致恶心呕吐（chemotherapy-induced nausea and vomiting，CINV）的随机对照试验（randomized controlled trials，RCTs），由2名评价员独立筛选文献、提取数据，并按照Cochrane偏倚风险评估工具评价文献质量，采用Stata 15.0统计软件进行网状meta分析。结果 共纳入18项RCTs，合计8 076例患者。网状meta分析结果显示：与5-HT₃+DEX比较，NEPA+DEX、NK-1RA+5-HT₃+DEX、NK-1RA+PAL+DEX和OLZ+PAL+DEX预防CINV急性完全缓解率高于5-HT₃+DEX组，差异有统计学意义（P<0.05），概率排序为OLZ+PAL+DEX > NK-1RA+PAL+DEX > NK-1RA+5-HT₃+DEX > NEPA+DEX > PAL+DEX=5-HT₃+DEX。与5-HT₃+DEX比较，NEPA+DEX、NK-1RA+5-HT₃+DEX、NK-1RA+PAL+DEX、OLZ+PAL+DEX和PAL+DEX预防CINV延迟期完全缓解率高于5-HT₃+DEX组，差异有统计学意义（P<0.05），概率排序为NK-1RA+PAL+DEX > OLZ+PAL+DEX > NEPA+DEX > NK-1RA+5-HT₃+DEX=PAL+DEX=5-HT₃+DEX。与5-HT₃+DEX比较，NEPA+DEX、NK-1RA+5-HT₃+DEX和NK-1RA+PAL+DEX预防CINV持续期完全缓解率高于5-HT₃+DEX组，差异有统计学意义（P<0.05），概率排序为NK-1RA+PAL+DEX > OLZ+PAL+DEX > NEPA+DEX > NK-1RA+5-HT₃+DEX > PAL+DEX > 5-HT₃+DEX。结论 通过网状meta分析发现，OLZ+PAL+DEX是预防HEC致急性CINV最有效方案，而NK-1RA+PAL+DEX是预防迟发性和持续期CINV最有效方案。

Abstract:

OBJECTIVE To evaluate the efficacy of six antiemetic regimens in the prevention of nausea and vomiting caused by highly emetogenic chemotherapy(HEC)by network meta analysis. METHODS Retrieved from CNKI, Wanfang database, VIP, PubMed, EMbase and Cochrane Library(Issue 8, 2019), retrieval time was limited to 1 September 2019. Randomized controlled trials(RCTs) about serotonin-3 receptor antagonist[include first-generation 5-HT₃ and second-generation 5-HT₃ palonosetron(PAL)]+dexamethasone(DEX), NK-1 receptor antagonist(NK-1RA)+5-HT₃+DEX, olanzapine(OLZ)+ 5-HT₃+DEX and NEPA(netupitant 300 mg+PAL 0.50 mg)+DEX in the prevention of chemotherapy-induced nausea and vomiting (CINV) were collected. The data were extracted by 2 evaluators and the quality of the literature was evaluated according to the cochrane bias risk assessment tool. The network meta-analysis was carried out by using Stata 15.0 statistical software. RESULTS A total of 18 RCTs were included, involving 8 076 patients. Results of network meta-analysis showed that:compared with 5-HT₃+DEX, NEPA+DEX, NK-1RA+5-HT₃+DEX, NK-1RA+PAL+DEX and OLZ+PAL+DEX could significantly improve CINV acute complete response, with statistical significance(P<0.05). The probability ranking was OLZ+PAL+DEX > NK-1RA+PAL+DEX > NK-1RA+5-HT₃+DEX > NEPA+DEX > PAL+DEX=5-HT₃+DEX. Compared with 5-HT₃+DEX, NEPA+DEX, NK-1RA+5-HT₃+ DEX, NK-1RA+PAL+DEX, OLZ+PAL+DEX and PAL+DEX could significantly improve CINV delayed complete response, with statistical significance(P<0.05). The probability ranking was NK-1RA+PAL+DEX > OLZ+PAL+DEX > NEPA+DEX > NK-1RA+5-HT₃+DEX=PAL+DEX=5-HT₃+DEX. Compared with 5-HT₃+DEX, NEPA+DEX, NK-1RA+5-HT₃+DEX and NK-1RA+PAL+DEX could significantly improve CINV overall complete response, with statistical significance(P<0.05). The probability ranking was NK-1RA+PAL+DEX > OLZ+PAL+DEX > NEPA+DEX > NK-1RA+5-HT₃+DEX > PAL+DEX > 5-HT₃+DEX. CONCLUSION By network meta-Analysis, OLZ+PAL+DEX is most likely to be the most effective intervention to prevent CINV caused by HEC, while NK-1RA+PAL+DEX is most likely to be the most effective intervention to prevent delayed and persistent CINV.