A Phase I Study to Characterize the Safety, Tolerability, and Pharmacokinetics of Topotecan at 4 mg/m² Administered Weekly as a 30-Minute Intravenous Infusion in Patients With Cancer

¹ Mayo Clinic
² GlaxoSmithKline

^* To whom correspondence should be addressed. E-mail: curtis.kelly1{at}mayo.edu.

	Abstract

Topotecan pharmacokinetics at higher infusion rates (4 mg/m² over 30 minutes) have not been studied. The authors report a pharmacokinetics and safety study of this dose in advanced cancer patients. Sixteen patients were given a 4-mg/m² topotecan infusion intravenously (IV) over 30 minutes weekly for 3 weeks, repeated every 28 days. Pharmacokinetics were determined after the first dose. Plasma concentrations of total topotecan were measured to derive CL, V, C, t, t_1/2, AUC_0-t, and AUC_0-. Plasma total topotecan concentrations decreased biexponentially, with a mean CL value of 20.6 L/h, V_ss value of 101 L, and t_1/2 value of 5.0 h. Nine significant adverse events (all hematologic) were topotecan related. Grade 3 or less adverse events included anemia, thrombocytopenia, leukopenia, and fatigue. Pharmacokinetics of the 4-mg/m² infusion of topotecan over 30 minutes are comparable to findings from studies of lower and higher doses. Toxicities are similar to previous reports.
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