Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting

Thomas M. Beck, Paul J. Hesketh, Stefan Madajewicz, Rudolph M. Navari, Kelly Pendergrass, Eric P. Lester, Julie A. Kish, William K. Murphy, John D. Hainsworth, David R. Gandara, Leslie J. Bricker, Alan M. Keller, Joanne Mortimer, Daniel V. Galvin, Karen W. House, Judy C. Bryson

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103 Scopus citations

Abstract

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 5 emetic episodes, withdrawn or rescued: high-dose, 20% v 34%; P = .018; medium-dose, 9% v 23%; P = .005).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.

Original languageEnglish (US)
Pages (from-to)1969-1975
Number of pages7
JournalJournal of Clinical Oncology
Volume10
Issue number12
StatePublished - 1992

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Beck, T. M., Hesketh, P. J., Madajewicz, S., Navari, R. M., Pendergrass, K., Lester, E. P., Kish, J. A., Murphy, W. K., Hainsworth, J. D., Gandara, D. R., Bricker, L. J., Keller, A. M., Mortimer, J., Galvin, D. V., House, K. W., & Bryson, J. C. (1992). Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting. Journal of Clinical Oncology, 10(12), 1969-1975.