This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zamboni, W. C. Articles by Tkaczuk, K. H. Search for Related Content PubMed PubMed Citation Articles by Zamboni, W. C. Articles by Tkaczuk, K. H.

Pharmacokinetic and Pharmacodynamic Study of the Combination of Docetaxel and Topotecan in Patients With Solid Tumors

From the Program of Molecular Therapeutics and Drug Discovery and Biostatistics Facility, University of Pittsburgh Cancer Institute; Department of Pharmaceutical Sciences, School of Pharmacy; Departments of Medicine and Pharmacology, School of Medicine; and Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; and Greenebaum Cancer Center, University of Maryland, Baltimore, MD.

Address reprint requests to William C. Zamboni, PharmD, University of Pittsburgh Cancer Institute, Biomedical Science Tower, E-1040, 200 Lothrop St, Pittsburgh, PA 15213; email zamboniwc{at}msx.upmc.edu

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 cycles 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.

This article has been cited by other articles:

				S. Dubey, P. Hutson, D. Alberti, R. Arzoomanian, K. Binger, J. Volkman, C. Feierabend, G. Wilding, and J. H Schiller Phase I study of docetaxel and topotecan in patients with advanced malignancies Journal of Oncology Pharmacy Practice, December 1, 2005; 11(4): 132 - 138. [Abstract] [PDF]

				M. S H Lam and R. J Ignoffo A guide to clinically relevant drug interactions in oncology Journal of Oncology Pharmacy Practice, June 1, 2003; 9(2-3): 45 - 85. [Abstract] [PDF]