Bone Marrow Transplant Program, Department of Pharmacy, University Medical Center, Maywood, Illinois, USA.
Biol Blood Marrow Transplant. 2013 Jan;19(1):49-55.e1. doi: 10.1016/j.bbmt.2012.07.019. Epub 2012 Aug 1.
Uncontrolled delayed nausea and vomiting remains a problem after high-dose preparative regimens used for autologous and allogeneic hematopoietic stem cell transplants. Recently, aprepitant was approved for highly and moderately emetogenic chemotherapy, and, in particular, is effective for decreasing delayed emesis. To evaluate its safety and efficacy in the transplantation setting, we performed a randomized, placebo-controlled, phase 3 trial of aprepitant in combination with ondansetron and dexamethasone in patients treated with ablative preparative regimens. Patients were randomized to receive oral aprepitant or placebo daily with oral ondansetron and dexamethasone during and for 3 days after the completion of the preparative regimen in this prospective randomized, double-blind study. The primary objective was complete response (CR) rate, defined as no emesis with no or mild nausea. Other endpoints included number of emetic episodes, nausea severity assessed using a 100-mm visual analog scale (VAS), the need for rescue antiemetics, and transplantation outcome, including regimen-related toxicity. One hundred eighty-one patients were randomized and 179 patients were eligible for analysis. Overall, CR rates were 81.9% for the aprepitant and 65.8% for the placebo arms (P < .001). Percentages of patients with no emesis all days were 73.3% for aprepitant and 22.5% placebo (P < .001). Mean VAS scores were 16.6 mm aprepitant and 16.9 mm placebo (NS), and there were no differences in the amount of rescue antiemetics used, regimen related toxicity, engraftment, or transplantation outcome. Aprepitant in combination with dexamethasone and ondansetron significantly decreased emesis and significant nausea, whereas not increasing RRT or affecting short-term survival but had no significant impact on the use of PRN antiemetics, or overall VAS nausea scores.
高剂量预处理方案用于自体和同种异体造血干细胞移植后，控制延迟性恶心和呕吐仍然是一个问题。最近，阿瑞匹坦被批准用于高度和中度致吐性化疗，特别是对减少延迟性呕吐有效。为了评估其在移植环境中的安全性和疗效，我们进行了一项随机、安慰剂对照、3 期阿瑞匹坦联合昂丹司琼和地塞米松治疗接受清除性预处理方案的患者的试验。在这项前瞻性随机、双盲研究中，患者随机接受口服阿瑞匹坦或安慰剂，同时口服昂丹司琼和地塞米松，在预处理方案完成期间和完成后 3 天内使用。主要终点是完全缓解（CR）率，定义为无呕吐且无或轻度恶心。其他终点包括呕吐发作次数、使用 100mm 视觉模拟量表（VAS）评估的恶心严重程度、需要抢救性止吐药以及移植结局，包括方案相关毒性。181 名患者随机分组，179 名患者符合分析条件。总体而言，阿瑞匹坦组的 CR 率为 81.9%，安慰剂组为 65.8%（P<0.001）。阿瑞匹坦组无呕吐的患者比例为 73.3%，安慰剂组为 22.5%（P<0.001）。阿瑞匹坦组的平均 VAS 评分为 16.6mm，安慰剂组为 16.9mm（无统计学差异），且使用抢救性止吐药、方案相关毒性、植入和移植结局无差异。阿瑞匹坦联合地塞米松和昂丹司琼可显著减少呕吐和明显恶心，而不增加 RRT 或影响短期生存，但对 PRN 止吐药的使用或总 VAS 恶心评分无显著影响。
