Perez E A, Navari R M, Kaplan H G, Gralla R J, Grunberg S M, Palmer R H, Fitts D
Mayo Clinic Jacksonville, FL 32224, USA.
Support Care Cancer. 1997 Jan;5(1):31-7. doi: 10.1007/BF01681959.
The purpose of this study was to evaluate the efficacy and safety of four different doses of granisetron when administered as a single intravenous (i.v.) dose for prophylaxis of cisplatin-induced emesis in a multicenter, randomized, parallel-group, double-blind investigation. A total of 353 chemotherapy-naive patients were enrolled, stratified according to cisplatin dose (moderate dose: 50-80 mg/m2, n = 169; high dose: 81-120 mg/m2, n = 184) and randomized to one of four granisetron doses: 5, 10, 20, or 40 micrograms/kg. Control of emesis was evaluated by the percentages of patients attaining complete response (no vomiting or retching, and no rescue medication) and major response (< or = 2 episodes of vomiting or retching, and no rescue medication). Patients were assessed on an inpatient basis for 18-24 h. Safety analyses consisted of adverse events and laboratory parameter changes. Complete response rates over 24 h after chemotherapy were 23%, 48%, 48%, and 44% for granisetron doses of 5, 10, 20, and 40 micrograms/kg, respectively, in the combined patient population (P = 0.011 for linear trend); 29%, 56%, 58%, and 41%, respectively, in the moderate-dose cisplatin stratum (P = 0.278 for linear trend); and 18%, 41%, 40%, and 47%, respectively, in the high-dose cisplatin stratum (P = 0.011 for linear trend). Transient headache was the most frequently reported adverse event (19%). There was no evidence of association between increased dose and headache. A single 10-, 20- or 40-micrograms/kg dose of granisetron is comparably effective in controlling nausea and vomiting associated with moderate or high-dose cisplatin chemotherapy. Granisetron was safe and well tolerated at all doses.
本研究旨在通过一项多中心、随机、平行组、双盲调查，评估四种不同剂量的格拉司琼单次静脉注射用于预防顺铂所致呕吐的疗效和安全性。共纳入353例未接受过化疗的患者，根据顺铂剂量（中等剂量：50 - 80mg/m²，n = 169；高剂量：81 - 120mg/m²，n = 184）进行分层，并随机分配至四种格拉司琼剂量组之一：5、10、20或40μg/kg。通过达到完全缓解（无呕吐或干呕，且未使用解救药物）和主要缓解（呕吐或干呕发作≤2次，且未使用解救药物）的患者百分比来评估呕吐控制情况。患者在住院基础上接受18 - 24小时评估。安全性分析包括不良事件和实验室参数变化。在联合患者群体中，格拉司琼剂量为5、10、20和40μg/kg时，化疗后24小时的完全缓解率分别为23%、48%、48%和44%（线性趋势P = 0.011）；在中等剂量顺铂组中分别为29%、56%、58%和41%（线性趋势P = 0.278）；在高剂量顺铂组中分别为18%、41%、40%和47%（线性趋势P = 0.011）。短暂性头痛是最常报告的不良事件（19%）。没有证据表明剂量增加与头痛之间存在关联。单次10、20或40μg/kg剂量的格拉司琼在控制与中等或高剂量顺铂化疗相关的恶心和呕吐方面效果相当。格拉司琼在所有剂量下均安全且耐受性良好。
