ORAL ONDANSETRON FOR THE CONTROL OF CISPLATIN-INDUCED DELAYED EMESIS - A LARGE, MULTICENTER, DOUBLE-BLIND, RANDOMIZED COMPARATIVE TRIAL OF ONDANSETRON VERSUS PLACEBO

Purpose: To investigate the efficacy and safety of oral ondansetron in the control of cisplatin-induced delayed emesis in patients who do not require rescue antiemetic therapy for acute emesis. Patients and Methods: Five hundred thirty-eight chemotherapy-naive patients who received cisplatin chemotherapy (greater than or equal to 70 mg/m(2)), and who were not rescued for acute emesis, were eligible to be randomized to receive one of three oral regimens to control delayed emesis, Group I received placebo on days 2 to 6; group II received ondansetron 8 mg twice daily on days 2 and 3 and placebo on days 4 to 6; group III received ondansetron 8 mg twice daily on days 2 to 6, All patients received intravenous ondansetron (0.15 mg/kg every 4 hours for three doses) for the control of acute emesis on day 1. The number of emetic episodes on days 2 cmd 3 combined (days 2/3, when incidence and severity of delayed emesis were expected to be greatest) was considered the primary measure of efficacy, Results: Patients who received odansetron had significantly fewer emetic episodes on days 2/3, 4, and 5 than those who received placebo (P less than or equal to .002 on each day). Additionally, significantly more patients who received ondansetron had a complete plus major response (C + MR; less than or equal to two emetic episodes) than those who received placebo on days 2/3 (56% v 37%, P = .001), 4 (94% v 85%, P = .005), and 5 (98% v 88%, P = .006). patients who received ondansetron had significantly less nausea on day 2/3 when day-1 nausea was used as the baseline score (P = .025). Patients who received ondansetron also had significantly less nausea on day 4 (P = .042) and the results approached significance on day 5 (P = .066). Conclusion: Oral ondansetron had a significant effect in the control of cisplatin-induced delayed emesis and nausea in patients who had not required rescue anti-emetics during the acute emesis period, The control of delayed nausea and vomiting was most notable in the immediate 2 days following cisplatin administration, with the clinical difference narrowing between the two treatment arms on subsequent days. (C) 1995 by American Society of Clinical Oncology.