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, Vss, Cmax, tmax, t 1/2, AUC0-t, and AUC0-ĝ̂. Plasma total topotecan concentrations decreased biexponentially, with a mean CL value of 20.6 L/h, Vss value of 101 L, and t1/2 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.
ASJC Scopus subject areas
- Pharmacology (medical)