Open-label comparison of the antiemetic efficacy of single intravenous doses of dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy

Autor: Mark L. Greenberg, Lewis C. Ingram, Robert Lau, Ronald D. Barr, Jean-Marie Leclerc, Maria Perrotta, Ronald Grant, Max J. Coppes, John Wiernikowski, Danny R. Howard, Ellen Dempsey
Rok vydání: 1999
Předmět:
Zdroj: Medical and Pediatric Oncology. 33:99-105
ISSN: 1096-911X
0098-1532
DOI: 10.1002/(sici)1096-911x(199908)33:2<99::aid-mpo7>3.0.co;2-p
Popis: Background. Nausea and vomiting are among the most unpleasant adverse side effects of cancer therapy. Procedure. An open-label dose-escalation study was conducted to assess the appropriate intravenous dose of dolasetron for pediatric patients undergoing chemotherapy. Patients received dolasetron in single intravenous doses of 0.6 (n = 10), 1.2 (n = 12), 1.8 (n = 12), or 2.4 (n = 12) mg/kg 30 min before receiving emetogenic chemotherapy. Pharmacokinetic parameters were evaluated at each dose level and efficacy was evaluated over the first 24 hr following the administration of dolasetron. Results. A complete response was achieved in 10% of patients given 0.6 mg/ kg, 25% of patients given 1.2 mg/kg, 67% of patients given 1.8 mg/kg, and 33% of patients given 2.4 mg/kg. Peak plasma concentrations (C max ) were observed between 0.33 and 0.75 hr following dolasetron infusion. C max and area under plasma concentration-time (AUC) increased with larger doses of dolasetron, while terminal disposition half-life (t 1/2 ) and apparent clearance (Cl app ) were not significantly changed with respect to dose. For 1.8-mg/kg dolasetron, the t 1/2 was 4.98 hr and the maximum plasma concentration (t max ) 0.47 hr. Adverse events were mild to moderate. No serious events occurred. Conclusions. This study suggests that a single intravenous dose of 1.8 mg/ kg is the optimum single intravenous dose for controlling chemotherapy-induced emesis in pediatric patients.
Databáze: OpenAIRE
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