Effects of prednisone on docetaxel pharmacokinetics in men with metastatic prostate cancer: A randomized drug–drug interaction study

Bodine P.S. Belderbos*, Koen G.A.M. Hussaarts, Leonie J. van Harten, Esther Oomen-de Hoop, Peter de Bruijn, Paul Hamberg, Robbert J. van Alphen, Brigitte C.M. Haberkorn, Martijn P. Lolkema, Ronald de Wit, Robert J. van Soest, Ron H.J. Mathijssen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

Abstract

Aims: Docetaxel has been approved for the treatment of metastatic prostate cancer in combination with prednisone. Since prednisone is known to induce the cytochrome P450 iso-enzyme CYP3A4, which is the main metabolizing enzyme of docetaxel in the liver, a potential drug–drug interaction may occur. In this prospective randomized pharmacokinetic cross-over study we investigated docetaxel exposure with concomitant prednisone, compared to docetaxel monotherapy in men with metastatic prostate cancer. Methods: Patients scheduled to receive at least 6 cycles of docetaxel (75 mg/m2) and who gave written informed consent were randomized to receive either the 1st 3 cycles, or the last 3 consecutive cycles with prednisone (twice daily 5 mg). Pharmacokinetic blood sampling was performed during cycle 3 and cycle 6. Primary endpoint was difference in docetaxel exposure, calculated as area under the curve (AUC0-inf) and analysed by means of a linear mixed model. Given the cross-over design the study was powered on 18 patients to answer the primary, pharmacokinetic, endpoint. Results: Eighteen evaluable patients were included in the trial. Docetaxel concentration with concomitant prednisone (AUC0-inf 2784 ng*h/mL, 95% confidence interval 2436–3183 ng*h/mL) was similar to the concentration of docetaxel monotherapy (AUC0-inf 2647 ng*h/mL, 95% confidence interval 2377–2949 ng*h/mL). Exploratory analysis showed no toxicity differences between docetaxel monotherapy and docetaxel cycles with prednisone. Conclusion: No significant difference in docetaxel concentrations was observed. In addition, we found similar toxicity profiles in absence and presence of prednisone. Therefore, from a pharmacokinetic point of view, docetaxel may be administrated with or without prednisone.

Original languageEnglish
Pages (from-to)986-992
Number of pages7
JournalBritish Journal of Clinical Pharmacology
Volume85
Issue number5
DOIs
Publication statusPublished - May 2019

Bibliographical note

Funding Information:
This work was supported by the Dutch Uro‐Oncology Group (DUOS)

Publisher Copyright:
© 2019 The British Pharmacological Society

Research programs

  • EMC MM-03-86-08

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