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

Autor: Belderbos BPS; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Hussaarts KGAM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van Harten LJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Oomen-de Hoop E; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., de Bruijn P; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Hamberg P; Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands., van Alphen RJ; Department of Internal Medicine, Elisabeth Twee Steden Ziekenhuis, Tilburg, The Netherlands., Haberkorn BCM; Department of Internal Medicine, Maasstad Ziekenhuis Rotterdam, The Netherlands., Lolkema MP; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., de Wit R; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van Soest RJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: British journal of clinical pharmacology [Br J Clin Pharmacol] 2019 May; Vol. 85 (5), pp. 986-992. Date of Electronic Publication: 2019 Mar 21.
DOI: 10.1111/bcp.13889
Abstrakt: 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/m 2 ) and who gave written informed consent were randomized to receive either the 1 st 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 (AUC 0-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 (AUC 0-inf 2784 ng*h/mL, 95% confidence interval 2436-3183 ng*h/mL) was similar to the concentration of docetaxel monotherapy (AUC 0-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.
(© 2019 The British Pharmacological Society.)
Databáze: MEDLINE
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