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

Kelly K. Curtis, Jean T. Hartney, Roxanne C. Jewell, Jung W. Park, Peter F. Lebowitz, Pamela P. Griffin, Mitesh J. Borad, Tom R. Fitch, Donald W. Northfelt

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7 Scopus citations

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, 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.

Original languageEnglish (US)
Pages (from-to)268-275
Number of pages8
JournalJournal of Clinical Pharmacology
Volume50
Issue number3
DOIs
StatePublished - Mar 1 2010

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Keywords

  • Intravenous
  • Pharmacokinetics
  • Safety
  • Topotecan
  • Weekly

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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