Open-label comparison of the antiemetic efficacy of single intravenous doses of dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy
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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 (Cmax) were observed between 0. 33 and 0.75 hr following dolasetron infusion. Cmax and area under plasma concentration-time (AUC) increased with larger doses of dolasetron, while terminal disposition half-life (t1/2) and apparent clearance (Clapp) were not significantly changed with respect to dose. For 1.8-mg/kg dolasetron, the t1/2 was 4.98 hr and the maximum plasma concentration (tmax) 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.