Aprepitant plus palonosetron versus dexamethasone plus palonosetron in preventing chemotherapy-induced nausea and vomiting in patients with moderate-emetogenic chemotherapy: A randomized, open-label, phase 3 trial.
Aprepitant plus palonosetron versus dexamethasone plus palonosetron in preventing chemotherapy-induced nausea and vomiting in patients with moderate-emetogenic chemotherapy: A randomized, open-label, phase 3 trial.
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阿瑞匹坦联合帕洛诺司琼与地塞米松联合帕洛诺司琼预防中度致吐化疗患者化疗诱导的恶心和呕吐：一项随机、开放标签、3期试验
DOI：
10.1016/j.eclinm.2022.101480
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发表时间：
2022-07
影响因子：
15.1
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管对于接受中度致吐化疗（MEC）的患者使用地塞米松联合帕洛诺司琼在预防化疗引起的恶心和呕吐（CINV）方面取得了显着进展，但其中一些患者仍然患有CINV。我们评估了阿瑞匹坦联合帕洛诺司琼是否可以提高接受 MEC 的患者预防 CINV 的疗效。这是一项单中心、开放标签、III期、随机对照试验，在中山大学附属第六医院进行。登记的患者计划接受 mFOLFOX6（奥沙利铂、亚叶酸和 5-氟尿嘧啶），但之前未接受过任何化疗。患者按 1:1 的比例随机分配到阿瑞匹坦组（第 1 天口服阿瑞匹坦 125 mg，第 2-3 天口服 80 mg）和地塞米松组（第 1 天静脉注射地塞米松 10 mg，第 2 和第 3 天静脉注射 5 mg），两组均在第 1 天静脉注射帕洛诺司琼 0.25 mg。主要终点是达到完全缓解 (CR) 的患者，定义为在整个阶段（0-120 小时）内没有呕吐且未使用救援药物。主要结局和安全性在修改后的意向治疗人群中进行评估，其中排除了所有在注册前 24 小时内使用艾司唑仑的患者以及拒绝记录恶心严重程度、呕吐频率和救援治疗使用情况的日记的患者。该试验已在 ClinicalTrials.gov 注册，NCT02909478。 2017年9月1日至2019年10月23日期间，入组了320名患者，并对315名患者进行了评估。在整个阶段（88.8% vs. 74.2%；P = 0.0010；比率差异，RD 15%，95% CI，6% 至 23%）和延迟阶段（25-120 小时），获得 CR 的患者比例显着高于地塞米松组，90.6% vs. 75.5%， （P < 0.0001；RD 15%，95% CI，7% 至 23%）。急性期（0-24 h）CR 率无显着差异，分别为 93.8% 与 93.5%（P = 0.94；RD 0%，95% CI，-5% 至 6%））。总体阶段，地塞米松组患者报告的失眠（P<0.0010）、消化不良（P=0.038）、潮红（P=0.0010）的发生率显着高于阿瑞吡坦组。在接受MEC方案mFOLFOX6的患者中，阿瑞匹坦联合帕洛诺司琼在预防CINV方面优于地塞米松联合帕洛诺司琼。国家重点研发计划（2019YFC1316000）和国家自然科学基金（81974369）。
Despite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) by using dexamethasone combined with palonosetron for patients who received moderate-emetogenic chemotherapy (MEC), some of these patients still suffer from CINV. We evaluated whether aprepitant combined with palonosetron can improve the efficacy in the prevention of CINV in patients receiving MEC. This was a single-centre, open-label, phase III, randomized controlled trial, which was done at the Sixth Affiliated Hospital of Sun Yat-sen University of China. The registered patients planned to receive mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) but had not received any chemotherapy previously. The patients were randomized in a 1:1 ratio to the aprepitant group (aprepitant 125 mg orally on day 1, 80 mg on day 2-3) and the dexamethasone group (dexamethasone 10 mg intravenously on day 1, 5 mg on days 2 and 3), both groups with palonosetron 0.25 mg intravenously on day 1. The primary endpoint was the proportion of patients who achieved a complete response (CR), defined as the absence of vomiting and no use of rescue medications in the overall phase (0–120 h). The primary outcome and safety were assessed in the modified intention-to-treat population, which excluded all patients who used estazolam within 24 h before registration and those who refused to keep a diary documenting the severity of nausea, frequency of vomiting, and the use of rescue therapy. This trial is registered with ClinicalTrials.gov, NCT02909478. Between Sep 1, 2017, and Oct 23, 2019, 320 patients were enrolled, and 315 patients were evaluated. The proportion of patients who achieved CR was significantly higher with aprepitant than that noted with dexamethasone in the overall phase (88.8% vs. 74.2%; P = 0.0010; rate difference, RD 15%, 95% CI, 6% to 23%) and in the delayed phase (25–120 h), 90.6% vs. 75.5%, (P < 0.0001; RD 15%, 95%CI, 7% to 23%). No significant difference of CR rate was observed in the acute phase (0–24 h), 93.8% vs. 93.5%, (P = 0.94; RD 0%, 95% CI, -5% to 6%)). In the overall phase, the incidence of insomnia (P < 0.0010), dyspepsia (P = 0.038), and flushing (P = 0.0010) reported by the patients was significantly higher in the dexamethasone group than that in the aprepitant group. Aprepitant combined with palonosetron is superior to dexamethasone combined with palonosetron in patients who received the MEC regimen mFOLFOX6 in terms of preventing CINV. The National Key R&D Program of China (2019YFC1316000) and the National Natural Science Foundation of China (81974369).
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