Single-Dose Fosaprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting Associated With Cisplatin Therapy: Randomized, Double-Blind Study Protocol-EASE
Single-Dose Fosaprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting Associated With Cisplatin Therapy: Randomized, Double-Blind Study Protocol-EASE
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DOI：
10.1200/jco.2010.31.7859
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发表时间：
2011-04-10
影响因子：
45.3
通讯作者：
Herrstedt, Jorn
中科院分区：
文献类型：
--
作者：
Grunberg, Steven;Chua, Daniel;Herrstedt, Jorn
目的在恩丹西酮和地塞米松方案的基础上加用神经激肽-1受体拮抗剂(NK1RA)，可有效预防化疗引起的恶心/呕吐(CINV)，尤其是在延迟期(DP；25-120小时)。因此，推荐的止吐方案包括多天服用NK1RA。初步数据显示，化疗前单次给药可在整个风险阶段(OP；0至120小时)提供CINV保护。这项研究比较了3天的口服复发剂方案和单次静脉注射NK1RA复发剂的方案。首次接受顺铂70 mg/m(2)的患者接受恩丹西酮和地塞米松的治疗，同时采用标准的顺铂方案(第一天125毫克，第二天80毫克，第三天80毫克)或单剂福司培南方案(第一天150毫克)。主要终点为完全缓解(CR；无呕吐，无抢救药物)。二次终点在DP期间为CR，在OP期间无呕吐。每个治疗组计划1,113名可评价患者，以确认非劣效性，预期CR为67.7%，非劣效性差值为-7个百分点。结果共随机分配2,322名患者，其中2,247名可评价疗效。在预定义的非劣势范围内，止吐保护与突起和突起相同。两种方案耐受性均较好，但在输液部位疼痛/红斑/血栓性静脉炎中，使用福司他汀的发生率较高(分别为2.7%和0.3%)。结论与恩丹西酮和地塞米松联合使用，单次静脉滴注福司普妥(150 Mg)预防OP和DP期间CINV的效果不亚于标准的3d口服福司他汀。
PurposeAddition of aprepitant, a neurokinin-1 receptor antagonist (NK1RA), to an ondansetron and dexamethasone regimen improves prevention of chemotherapy-induced nausea/vomiting (CINV), particularly during the delayed phase (DP; 25 to 120 hours). Therefore, recommended antiemetic regimens include multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous NK1RA fosaprepitant.Patients and MethodsA randomized, double-blind, active-control design was used to test whether fosaprepitant is noninferior to aprepitant. Patients receiving cisplatin >= 70 mg/m(2) for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1). The primary end point was complete response (CR; no vomiting, no rescue medication) during OP. Secondary end points were CR during DP and no vomiting during OP. Accrual of 1,113 evaluable patients per treatment arm was planned to confirm noninferiority with expected CR of 67.7% and noninferiority margin of minus 7 percentage points.ResultsA total of 2,322 patients were randomly assigned, and 2,247 were evaluable for efficacy. Antiemetic protection with aprepitant and fosaprepitant was equivalent within predefined bounds for noninferiority. Both regimens were well tolerated, although more frequent infusion site pain/erythema/thrombophlebitis was seen with fosaprepitant relative to aprepitant (2.7% v 0.3%, respectively).ConclusionGiven with ondansetron and dexamethasone, single-dose intravenous fosaprepitant (150 mg) was noninferior to standard 3-day oral aprepitant in preventing CINV during OP and DP.