Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, 535 Barnhill Dr, RT #473, Indianapolis, IN 46202, USA.
J Clin Oncol. 2012 Nov 10;30(32):3998-4003. doi: 10.1200/JCO.2011.39.5558. Epub 2012 Aug 20.
Aprepitant, a 5-HT3 receptor antagonist (5HT3-RA), and dexamethasone are standard antiemetic therapy for prevention of single-day, cisplatin-induced nausea and vomiting. We conducted a double-blind, placebo-controlled phase III cross-over study that compared aprepitant to placebo combined with standard antiemetic prophylaxis (a 5HT3-RA and dexamethasone) in patients receiving 5 days of cisplatin combination chemotherapy for testicular cancer.
Patients receiving two consecutive identical courses of a 5-day cisplatin-based chemotherapy were randomly assigned to aprepitant 125 mg on day 3 and 80 mg per day on days 4 through 7 or to placebo with the initial course and crossover to the opposite treatment with the second course. The primary objective was complete response (CR). Secondary end points were emetic episodes (acute and delayed), nausea measurement based on a visual analog scale (VAS), and patient-stated preference after the second study cycle.
In all, 71 patients were screened for the study and 69 were evaluable. Thirty-five patients were randomly assigned to receive aprepitant and 34 to receive placebo for the first course. Forty-two percent achieved CR with aprepitant compared with 13% with placebo (P < .001). Eleven patients (16.2%) had at least one emetic episode during the aprepitant cycle versus 32 patients (47.1%) with placebo. Thirty-eight patients preferred the aprepitant cycle whereas 11 preferred placebo (P < .001). There was no statistical difference in VAS for nausea, but it was numerically superior with aprepitant. There was no toxicity with aprepitant compared with placebo.
There was a significant improvement in CR rate with aprepitant combined with a 5HT3-RA and dexamethasone. Patient preference strongly favored the aprepitant cycle.
阿瑞匹坦是一种 5-羟色胺 3 受体拮抗剂（5-HT3-RA）和地塞米松，是预防单日内顺铂引起的恶心和呕吐的标准止吐治疗药物。我们进行了一项双盲、安慰剂对照的 III 期交叉研究，比较了阿瑞匹坦与安慰剂联合标准止吐预防（5-HT3-RA 和地塞米松）在接受 5 天顺铂联合化疗治疗睾丸癌的患者中的疗效。
接受两剂连续相同的 5 天顺铂化疗的患者随机分配到阿瑞匹坦 125mg 第 3 天和 80mg 每天第 4 天至第 7 天或安慰剂的初始疗程，然后交叉到第二疗程的相反治疗。主要终点是完全缓解（CR）。次要终点是呕吐发作（急性和延迟）、基于视觉模拟量表（VAS）的恶心测量和第二研究周期后患者的偏好。
共有 71 名患者接受了研究筛选，69 名患者可评估。35 名患者随机接受阿瑞匹坦治疗，34 名患者接受安慰剂治疗第一疗程。阿瑞匹坦组有 35 名患者（42%）达到 CR，而安慰剂组有 5 名患者（13%）（P<.001）。阿瑞匹坦组有 11 名患者（16.2%）发生至少一次呕吐发作，而安慰剂组有 32 名患者（47.1%）。38 名患者更喜欢阿瑞匹坦周期，而 11 名患者更喜欢安慰剂（P<.001）。虽然阿瑞匹坦组的恶心 VAS 评分没有统计学差异，但它在数值上优于安慰剂组。与安慰剂相比，阿瑞匹坦没有毒性。
阿瑞匹坦联合 5-HT3-RA 和地塞米松治疗可显著提高 CR 率。患者的偏好强烈倾向于阿瑞匹坦周期。
