Cheng Yi, Wu Zehua, Shi Lishuo, Shen Cailu, Zhang Jianwei, Hu Huabin, Li Weiwei, Cai Yue, Xie Xiaoyu, Ling Jiayu, Zheng Qin, Deng Yanhong
Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University No. 26, Yuancunerheng Road, Guangzhou 510655, China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
EClinicalMedicine. 2022 Jun 3;49:101480. doi: 10.1016/j.eclinm.2022.101480. eCollection 2022 Jul.
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%; = 0.0010; rate difference, RD 15%, 95% CI, 6% to 23%) and in the delayed phase (25-120 h), 90.6% vs. 75.5%, ( < 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%, ( = 0.94; RD 0%, 95% CI, -5% to 6%)). In the overall phase, the incidence of insomnia ( < 0.0010), dyspepsia ( = 0.038), and flushing ( = 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).
尽管使用地塞米松联合帕洛诺司琼预防接受中度致吐性化疗（MEC）患者的化疗引起的恶心和呕吐（CINV）取得了显著进展，但这些患者中的一些人仍遭受CINV困扰。我们评估了阿瑞匹坦联合帕洛诺司琼是否能提高接受MEC患者预防CINV的疗效。
这是一项在中国中山大学附属第六医院进行的单中心、开放标签、III期随机对照试验。登记的患者计划接受mFOLFOX6（奥沙利铂、亚叶酸钙和5-氟尿嘧啶）治疗，但之前未接受过任何化疗。患者按1:1比例随机分为阿瑞匹坦组（第1天口服阿瑞匹坦125mg，第2 - 3天口服80mg）和地塞米松组（第1天静脉注射地塞米松10mg，第2天和第3天静脉注射5mg），两组均在第1天静脉注射帕洛诺司琼0.25mg。主要终点是达到完全缓解（CR）的患者比例，定义为在整个阶段（0 - 120小时）无呕吐且未使用解救药物。在改良意向性治疗人群中评估主要结局和安全性，该人群排除了登记前24小时内使用艾司唑仑的所有患者以及拒绝记录恶心严重程度、呕吐频率和解救治疗使用情况的患者。本试验已在ClinicalTrials.gov注册，注册号为NCT02909478。
在2017年9月1日至2019年10月23日期间，共纳入320例患者，其中315例患者接受评估。在整个阶段（88.8%对74.2%；P = 0.0010；率差，RD 15%，95%CI，6%至23%）和延迟阶段（25 - 120小时），阿瑞匹坦组达到CR的患者比例显著高于地塞米松组，分别为90.6%对75.5%，（P < 0.0001；RD 15%，95%CI，7%至23%）。在急性期（0 - 24小时）未观察到CR率的显著差异，分别为93.8%对93.5%，（P = 0.94；RD 0%，95%CI， - 5%至6%）。在整个阶段，地塞米松组患者报告的失眠（P < 0.0010）、消化不良（P = 0.038）和潮红（P = 0.0010）发生率显著高于阿瑞匹坦组。
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。
中国国家重点研发计划（2019YFC1316000）和中国国家自然科学基金（81974369）。
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