Pharmacokinetic and pharmacodynamic study of the combination of docetaxel and topotecan in patients with solid tumors

William C. Zamboni, Merrill J.M. Egorin, David A.V. Van Echo, Roger S.D. Day, Barry R.M. Meisenberg, Sandra E. Brooks, L. Austin Doyle, Noble N. Nemieboka, Jason M. Dobson, Nancy S. Tait, Katherine H. Tkaczuk

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Abstract

Purpose: The sequence in which chemotherapeutic agents are administered can alter their pharmacokinetics, therapeutic effect, and toxicity. We evaluated the pharmacokinetics and pharmacodynamics of docetaxel and topotecan when coadministered on two different sequences of administration. Patients and Methods: On cycle 1, docetaxel was administered as a 1-hour infusion at 60 mg/m2 without filgrastim and at 60, 70, and 80 mg/m2 with filgrastim on day 1, and topotecan was administered at 0.75 mg/m2 as a 0.5-hour infusion on days 1 to 4. On cycle 2, topotecan was administered on days 1 to 4, and docetaxel was administered on day 4. Cycles were repeated every 21 days. Blood samples for high-performance liquid chromatography measurement of docetaxel (CL(DOC)) and topotecan (CL(TPT)) total clearance were obtained on day 1 of cycle 1 and day 4 of cycle 2. CL(DOC) and CL(TPT) were calculated using compartmental methods. Results: Mean ± SD CL(DOC) in cycles 1 and 2 were 75.9 ± 79.6 L/h/m2 and 29.2 ± 17.3 L/h/m2, respectively (P < .046). Mean ± SD CL(TPT) in cyles 1 and 2 were 8.5 ± 4.4 L/h/m2 and 9.3 ± 3.4 L/h/m2, respectively (P > .05). Mean ± SD neutrophil nadir in cycles 1 and 2 were 4,857 ± 6,738/μL and 2,808 ± 4,518/μL, respectively (P = .02). Conclusion: Administration of topotecan on days 1 to 4 and docetaxel on day 4 resulted in an approximately 50% decrease in docetaxel clearance and was associated with increased neutropenia. (C) 2000 by American Society of Clinical Oncology.

Original languageEnglish (US)
Pages (from-to)3288-3294
Number of pages7
JournalJournal of Clinical Oncology
Volume18
Issue number18
DOIs
StatePublished - Sep 15 2000

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zamboni, W. C., Egorin, M. J. M., Van Echo, D. A. V., Day, R. S. D., Meisenberg, B. R. M., Brooks, S. E., Doyle, L. A., Nemieboka, N. N., Dobson, J. M., Tait, N. S., & Tkaczuk, K. H. (2000). Pharmacokinetic and pharmacodynamic study of the combination of docetaxel and topotecan in patients with solid tumors. Journal of Clinical Oncology, 18(18), 3288-3294. https://doi.org/10.1200/JCO.2000.18.18.3288