Smith D B, Newlands E S, Rustin G J, Begent R H, Howells N, McQuade B, Bagshawe K D
Department of Medical Oncology, Charing Cross Hospital, London, UK.
Lancet. 1991 Aug 24;338(8765):487-90. doi: 10.1016/0140-6736(91)90555-4.
Ondansetron, a serotonin antagonist, is effective in controlling the emesis associated with cancer chemotherapy; however, emesis in patients receiving high-dose cisplatin is poorly controlled by ondansetron alone. Dexamethasone is an effective antiemetic with no known interaction with serotonin receptors and was thus chosen for study in combination with ondansetron. 31 patients (30 male, 1 female; median age 28.5 years, range 18-49) receiving a 4-day course of a chemotherapy regimen containing cisplatin (100-120 mg/m2) for metastatic germ-cell tumours were entered in a randomised, double-blind, cross-over trial comparing oral ondansetron plus placebo with oral ondansetron plus dexamethasone as antiemetic prophylaxis. Ondansetron (8 mg every 8 h) was given to all patients for 8 days from the start of chemotherapy. Patients were given 8 mg of dexamethasone or placebo every 8 h starting 2 h before cisplatin (on day 4) and continuing for six doses (ie, for 2 days only). A second course of chemotherapy began 14 days after the start of the first, during which patients crossed over to the alternative antiemetic regimen. Results were available from 27 patients. In the 24-48 h after cisplatin 78% of patients taking ondansetron plus dexamethasone reported complete or major control of emesis compared with 30% of those taking ondansetron plus placebo (p = 0.001). Cross-over analysis showed a significant advantage for ondansetron plus dexamethasone in the control of nausea (p = 0.013) and emesis (p less than 0.001) over the 8-day study. 24 of 26 patients expressed a preference for the combination therapy (p less than 0.001). Ondansetron plus dexamethasone is effective antiemetic prophylaxis for high-dose cisplatin chemotherapy, has few side effects, and is active when given orally.
昂丹司琼是一种5-羟色胺拮抗剂，对控制癌症化疗相关的呕吐有效；然而，对于接受大剂量顺铂治疗的患者，单用昂丹司琼对呕吐的控制效果不佳。地塞米松是一种有效的止吐药，与5-羟色胺受体无已知相互作用，因此被选来与昂丹司琼联合进行研究。31例接受含顺铂（100 - 120mg/m²）的4天化疗方案治疗转移性生殖细胞肿瘤的患者（30例男性，1例女性；年龄中位数28.5岁，范围18 - 49岁）进入一项随机、双盲、交叉试验，比较口服昂丹司琼加安慰剂与口服昂丹司琼加地塞米松作为止吐预防措施的效果。从化疗开始，所有患者均给予昂丹司琼（每8小时8mg），共8天。在顺铂给药前2小时（第4天）开始，每8小时给予患者8mg地塞米松或安慰剂，并持续给予6剂（即仅持续2天）。第一个疗程开始14天后开始第二个化疗疗程，在此期间患者交叉使用另一种止吐方案。27例患者有结果。在顺铂给药后的24 - 48小时内，服用昂丹司琼加地塞米松的患者中有78%报告呕吐得到完全或主要控制，而服用昂丹司琼加安慰剂的患者中这一比例为30%（p = 0.001）。交叉分析显示，在为期8天的研究中，昂丹司琼加地塞米松在控制恶心（p = 0.013）和呕吐（p＜0.001）方面比单用昂丹司琼有显著优势。26例患者中有24例表示更喜欢联合治疗（p＜0.001）。昂丹司琼加地塞米松是大剂量顺铂化疗有效的止吐预防措施，副作用少，口服时也有活性。
