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

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.