STRATIFIED, RANDOMIZED, DOUBLE-BLIND COMPARISON OF INTRAVENOUS ONDANSETRON ADMINISTERED AS A MULTIPLE-DOSE REGIMEN VERSUS 2 SINGLE-DOSE REGIMENS IN THE PREVENTION OF CISPLATIN-INDUCED NAUSEA AND VOMITING

Purpose: This study compares the efficacy and safety of two single-dose regimens with the approved three-dose regimen of ondansetron in the prevention of cisplatin-induced emesis. Patients and Methods: This multicenter study was a stratified, randomized, double-blind, and parallel group design. Chemotherapy-naive inpatients were randomized to receive intravenous (IV) ondansetron (Zofran; Glaxo Inc, Research Triangle Park, NC) 0.15 mg/kg times three doses, every 4 hours or a single 8-mg or 32-mg dose followed by two saline doses that began 30 minutes before cisplatin administration. Cisplatin (high-dose ≥ 100 mg/m2 or medium-dose 50 to 70 mg/m2) was given as a single infusion (≤ 3 hours). Patients were monitored for emetic episodes, adverse events, and laboratory safety parameters for 24 hours after cisplatin administration. Results: A total of 699 patients (359 high-dose, 340 medium-dose) were enrolled. Of these, 618 were assessable for efficacy (15 ineligible, 66 protocol deviations). The 32-mg dose was superior to the 8-mg single dose with regard to total number of emetic episodes (high-dose, P = .015; medium-dose, P < .001), complete response (no emetic episodes: high-dose, 48% v 35%; P = .048; medium-dose, 73% v 50%; P = .001) and failure rate (> 5 emetic episodes, withdrawn or rescued: high-dose, 20% v 34%; P = .018; medium-dose, 9% v 23%; P = .005). The 32-mg single dose was also superior to the 0.15 mg/kg times three dose regimen with regard to total number of emetic episodes (medium-dose, P = .033) and failure rate (high-dose, 20% v 36%; P = .009; medium-dose, 9% v 22%; P = .011). Ondansetron was well tolerated. The most common adverse event was headache. An approximate 10-fold increase in the incidence of clinically significant transaminase elevations was observed in the high-dose versus medium-dose cisplatin strata (asparate aminotransferase [AST], 6.5% v 0.7%; serum alanine aminotransferase [ALT], 5.0% v 0.3%). Conclusion: A 32-mg single dose of ondansetron is more effective than a single 8-mg dose and is at least as effective as the standard regimen of 0.15 mg/kg times three doses in the prevention of cisplatin-induced acute emesis. © 1992 by American Society of Clinical Oncology.