Cubeddu L X, Hoffmann I S, Fuenmayor N T, Finn A L
Department of Pharmacology, University of North Carolina, Chapel Hill.
N Engl J Med. 1990 Mar 22;322(12):810-6. doi: 10.1056/NEJM199003223221204.
We compared the efficacy and safety of ondansetron (GR 38032F), a selective antagonist of serotonin S3 receptors, with that of placebo in controlling the nausea and vomiting induced by cisplatin treatment in 28 patients with cancer. The patients received either three intravenous doses of ondansetron (0.15 mg per kilogram of body weight) or normal saline (placebo) at four-hour intervals, beginning 30 minutes before the administration of cisplatin. Nausea and vomiting were markedly diminished in the group given ondansetron. The median time to the first episode of emesis was 2.8 hours in the placebo group and 11.6 hours in the ondansetron group (P less than 0.001); the median number of episodes in 24 hours was 5.5 in the placebo group and 1.5 in the ondansetron group (P less than 0.001); the mean (+/- SEM) number of regurgitations or dry heaves per episode was 3.2 +/- 0.5 in the placebo group and 1.17 +/- 0.1 in the ondansetron group (P less than 0.001). None of the 14 patients given ondansetron, but 12 of 14 given placebo, required treatment with antiemetic-rescue agents for the control of nausea and vomiting. There were no adverse effects attributable to ondansetron. The urinary excretion of 5-hydroxyindoleacetic acid, the main metabolite of serotonin, was increased in all patients two to six hours after they received cisplatin chemotherapy, and the increases paralleled the episodes of emesis. We conclude that ondansetron is an effective and safe agent for controlling the nausea and vomiting induced by cisplatin treatment. We suggest that cisplatin treatment increases the release of serotonin from enterochromaffin cells, and that ondansetron acts by blocking S3 receptors for serotonin.
我们比较了5-羟色胺S3受体选择性拮抗剂昂丹司琼（GR 38032F）与安慰剂在控制28例癌症患者顺铂治疗所致恶心和呕吐方面的疗效及安全性。患者在顺铂给药前30分钟开始，每4小时接受3次静脉注射昂丹司琼（0.15毫克/千克体重）或生理盐水（安慰剂）。接受昂丹司琼治疗的组中恶心和呕吐明显减轻。安慰剂组首次呕吐发作的中位时间为2.8小时，昂丹司琼组为11.6小时（P<0.001）；安慰剂组24小时内呕吐发作的中位次数为5.5次，昂丹司琼组为1.5次（P<0.001）；安慰剂组每次反流或干呕的平均（±标准误）次数为3.2±0.5次，昂丹司琼组为1.17±0.1次（P<0.001）。接受昂丹司琼治疗的14例患者中无一例需要用止吐解救药物来控制恶心和呕吐，而接受安慰剂治疗的14例患者中有12例需要。未发现与昂丹司琼相关的不良反应。所有患者在接受顺铂化疗后2至6小时，5-羟色胺的主要代谢产物5-羟吲哚乙酸的尿排泄量均增加，且增加情况与呕吐发作平行。我们得出结论，昂丹司琼是控制顺铂治疗所致恶心和呕吐的一种有效且安全的药物。我们认为顺铂治疗会增加肠嗜铬细胞中5-羟色胺的释放，而昂丹司琼通过阻断5-羟色胺的S3受体发挥作用。
