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 (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. Med. Pediatr. Oncol. 33:99-105, 1999.

Electrocardiographic findings after 5‐HT3 receptor antagonists and chemotherapy in children with cancer

“…Recently, Gupta et al [28] described prolongation of dispersion of QT and QTc intervals after anthracycline therapy for childhood malignancies even in the presence of normal QT and QTc intervals on ECG. Coppes et al [29] demonstrated asymptomatic increases at 1 hr posttreatment in the PR, QRS, QT, and QTc intervals in four different intravenous doses groups of dolasetron mesylate in children receiving chemotherapy. These increases were considered mild in intensity and without clinical significance.…”

A review of dolasetron as management of nausea and vomiting in cancer patients

“…Pediatric population An open -label dose -escalation study by Coppes et al 28 evaluated four doses of iv dolasetron ( 0.6, 1.2, 1.8, 2.4 mg / kg ) in 46 pediatric patients ( 3± 18 years of age ) receiving moderately to highly emetogenic chemotherapy and experiencing acute emesis. The CR rates were 10% ( 1 of 10 ) , 25% ( 3 of 12 ) , 67% ( 8 of 12 ) , and 33% ( 4 of 12 ) , respectively.…”