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

Research output: Contribution to journalArticle

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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 2010

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Topotecan
Intravenous Infusions
Pharmacokinetics
Safety
Neoplasms
Leukopenia
Thrombocytopenia
Fatigue
Anemia

Keywords

  • Intravenous
  • Pharmacokinetics
  • Safety
  • Topotecan
  • Weekly

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

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

In: Journal of Clinical Pharmacology, Vol. 50, No. 3, 03.2010, p. 268-275.

Research output: Contribution to journalArticle

Curtis, Kelly K. ; Hartney, Jean T. ; Jewell, Roxanne C. ; Park, Jung W. ; Lebowitz, Peter F. ; Griffin, Pamela P. ; Borad, Mitesh J ; Fitch, Tom R. ; Northfelt, Donald W. / 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. In: Journal of Clinical Pharmacology. 2010 ; Vol. 50, No. 3. pp. 268-275.
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