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

Abstract

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.

• Authors: M J Coppes, R Lau, L C Ingram, J T Wiernikowski, R Grant, D R Howard, M Perrotta, R Barr, E Dempsey, M L Greenberg, J M Leclerc
• Journal: Medical and pediatric oncology (Med Pediatr Oncol) Vol. 33 Issue 2 Pg. 99-105 (Aug 1999) ISSN: 0098-1532 [Print] United States
• PMID: 10398184 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 1999 Wiley-Liss, Inc.

Chemical References

• Antiemetics
• Antineoplastic Agents
• Indoles
• Quinolizines
• Serotonin Antagonists
• dolasetron

Topics

• Adolescent
• Antiemetics (administration & dosage, pharmacokinetics, therapeutic use)
• Antineoplastic Agents (adverse effects)
• Area Under Curve
• Child
• Child, Preschool
• Female
• Humans
• Indoles (administration & dosage, pharmacokinetics, therapeutic use)
• Infusions, Intravenous
• Male
• Nausea (chemically induced, prevention & control)
• Neoplasms (drug therapy)
• Quinolizines (administration & dosage, pharmacokinetics, therapeutic use)
• Serotonin Antagonists (administration & dosage, pharmacokinetics, therapeutic use)
• Vomiting (chemically induced, prevention & control)