EFFECT OF SCHEDULE AND MAINTENANCE ON THE ANTIEMETIC EFFICACY OF ONDANSETRON COMBINED WITH DEXAMETHASONE IN ACUTE AND DELAYED NAUSEA AND EMESIS IN PATIENTS RECEIVING MODERATELY EMETOGENIC CHEMOTHERAPY - A PHASE-III TRIAL BY THE NATIONAL-CANCER-INSTITUTE OF CANADA CLINICAL-TRIALS GROUP

Purpose: This study examines whether the schedule of ondansetron significantly influences its antiemetic efficacy in the first 24 hours after chemotherapy, whether the administration of oral ondansetron after 24 hours is effective in preventing delayed emesis, and whether the efficacy of ondansetron is preserved over multiple courses of moderately emetogenic chemotherapy. Patients and Methods: A multicenter double-blind study randomized 302 cancer patients to one of three treatment arms. Arm A received dexamethasone 10 mg intravenously (IV) plus ondansetron (Zofran; Glaxo Canada Inc, Toronto, Canada) 8 mg IV prechemotherapy plus ondansetron 8 mg orally every 12 hours postchemotherapy for nine doses. Arm B received dexamethasone 10 mg IV plus ondansetron 16 mg IV prechemotherapy plus placebo orally postchemotherapy in the same schedule as arm A. Arm C received dexamethasone 10 mg IV plus ondansetron 8 mg prechemotherapy plus ondansetron 8 mg orally postchemotherapy for one dose followed by placebo orally every 12 hours for eight more doses. Response was assessed by the number of reported episodes of vomiting and by severity of nausea measured on a visual analog scale (VAS). Results: The two schedules of ondansetron used in the first 24 hours were no different in their antiemetic efficacy, with similar rates for complete responses (76.7% v 72.0%, P = .472), complete plus major responses (90.2% v 82.0%, P = .135), and severity of nausea (P = .348). Oral ondansetron after 24 hours was more effective than placebo in preventing delayed nausea and emesis, with superior rates of complete responses (59.6% v 42.1%, P = .012 by one-sided test), complete plus major responses (80.9% v 66.3%, P = .018 by one-sided test), and less severe nausea (9.2 mm v 18.6 mm on a 100-mm VAS, P = .002). The efficacy of ondansetron was maintained over subsequent courses of chemotherapy. Conclusion: The schedule of ondansetron in the first 24 hours does not influence its efficacy. The use of oral maintenance ondansetron is effective in preventing delayed nausea and emesis after moderately emetogenic chemotherapy.