Bey P, Wilkinson P M, Resbeut M, Bourdin S, Le Floch O, Hahne W, Claverie N
Centre Alexis Vautrin, Vandoeuvre-Les-Nancy, France.
Support Care Cancer. 1996 Sep;4(5):378-83. doi: 10.1007/BF01788845.
The aim of this work was to measure the safety and efficacy of single i.v. doses of dolasetron mesilate for the control of emesis caused by single high-dose (at least 6 Gy) radiotherapy to the upper abdomen. The double-blind, placebo-controlled, multicenter study stratified patients on the basis of being naive or nonnaive to radiotherapy. Patients with or without a history of previous chemotherapy were enrolled. Patients were randomized to receive placebo or 0.3, 0.6, or 1.2 mg/kg dolasetron mesilate 30 min before radiotherapy, then monitored for 24 h. Antiemetic efficacy was assessed from the time to the first emetic episode or rescue, from whether there was a complete response (0 emetic episodes /no rescue medication) or a complete-plus-major response (0-2 emetic episodes/no rescue medication), from the severity of nausea (rated by patients and the investigator), and from the investigator's assessment of efficacy. Fifty patients completed the study (owing to changing medical practice, enrollment objectives were not met; consequently, no significant linear dose trend was expected). Pooled dolasetron was superior to the placebo in its effect on the time to first emesis or rescue in radiotherapy-nonnaive patients (P = 0.015). Dolasetron was statistically superior to the placebo in the overall population on the basis of a complete plus major response: 54%, 100%, 93%, and 83% for the placebo and 0.3-, 0.6-, and 1.2-mg/kg doses respectively (P = 0.002). The low response in the highest dose group may be due to an imbalance in the number of chemotherapy-nonnaive patients in that group. Dolasetron was superior to the placebo on the basis of nausea assessed by the investigator (P = 0.024) and administration of rescue medication (P = 0.006). Complete response at the 0.3-mg/ kg dose was superior to results with the placebo (P = 0.050). Treatment-related adverse events were rare, mild to moderate in intensity, and evenly distributed across the four groups. Overall, dolasetron mesilate was effective and well-tolerated in the control of single, high-dose radiotherapy-induced emesis.
本研究旨在测定静脉注射单剂量甲磺酸多沙普仑控制上腹部单次大剂量（至少6 Gy）放疗所致呕吐的安全性和有效性。这项双盲、安慰剂对照、多中心研究根据患者是否初次接受放疗对患者进行分层。纳入有或无既往化疗史的患者。患者在放疗前30分钟随机接受安慰剂或0.3、0.6或1.2 mg/kg甲磺酸多沙普仑，然后监测24小时。通过首次呕吐发作或急救时间、是否有完全缓解（0次呕吐发作/未使用急救药物）或完全加主要缓解（0 - 2次呕吐发作/未使用急救药物）、恶心严重程度（由患者和研究者评定）以及研究者对疗效的评估来评价止吐疗效。50名患者完成了研究（由于医疗实践的变化，未达到入组目标；因此，预计不存在显著的线性剂量趋势）。在初次接受放疗的患者中，合并使用多沙普仑在首次呕吐或急救时间方面的效果优于安慰剂（P = 0.015）。基于完全加主要缓解，在总体人群中多沙普仑在统计学上优于安慰剂：安慰剂组以及0.3、0.6和1.2 mg/kg剂量组的缓解率分别为54%、100%、93%和83%（P = 0.002）。最高剂量组缓解率较低可能是由于该组中未接受过化疗的患者数量不均衡。根据研究者评定的恶心情况（P = 0.024）和急救药物使用情况（P = 0.006），多沙普仑优于安慰剂。0.3 mg/kg剂量组的完全缓解率优于安慰剂组（P = 0.050）。与治疗相关的不良事件罕见，强度为轻至中度，且在四组中分布均匀。总体而言，甲磺酸多沙普仑在控制单次大剂量放疗引起的呕吐方面有效且耐受性良好。
