Open-label comparison of the antiemetic efficacy of single intravenous doses of dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy
✍ Scribed by Coppes, Max J.; Lau, Robert; Ingram, Lewis C.; Wiernikowski, John T.; Grant, Ronald; Howard, Danny R.; Perrotta, Maria; Barr, Ronald; Dempsey, Ellen; Greenberg, Mark L.; Leclerc, Jean-Marie
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 81 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0098-1532
No coin nor oath required. For personal study only.
✦ Synopsis
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.