Abstract 3419
Background
In metastatic hormone-naïve prostate cancer it is currently unclear whether docetaxel chemotherapy should be administered with or without prednisone. Furthermore, the role of corticosteroids in metastatic castration-resistant prostate cancer is controversial, concerning its limited effect on chemotherapy-induced toxicities, small biological anti-tumor effect on PSA-response, and potential toxicity of long-term use. Prednisone is known to induce CYP3A4, which metabolizes taxanes, resulting in a possible drug-drug interaction (DDI). Therefore, we investigated the pharmacological aspects of the addition of prednisone to docetaxel chemotherapy in men with metastatic prostate cancer.
Methods
We conducted a prospective randomized pharmacokinetic (PK) cross-over study in metastatic prostate cancer patients, who received 6 cycles of docetaxel (Q3W, 75mg/m2), in which prednisone was added to 3 consecutive chemotherapy cycles. These were followed or preceded (determined by randomization) by 3 consecutive cycles of docetaxel monotherapy. Blood sampling for PK purposes occurred during cycle 3 and cycle 6. Primary endpoint was the difference in docetaxel exposure (AUC0-inf) with concomitant prednisone, compared to exposure of docetaxel monotherapy by means of a linear mixed model analysis on log-transformed data.
Results
Eighteen patients were evaluable for the primary endpoint. Docetaxel exposure with concomitant prednisone (geomean AUC0-inf 2784 ng*h/mL, CV 27%) was slightly higher (1.8%; 95% CI -9.9% till 15.2%, p = 0.75) as compared to docetaxel monotherapy (geomean AUC0-inf 2647 ng*h/mL, CV 22%). Toxicity rates were similar for docetaxel cycles with and without prednisone.
Conclusions
No difference in docetaxel pharmacokinetics in cycles with or without prednisone was observed. Moreover, we found similar toxicity profiles in the docetaxel cycles with concomitant prednisone as in the docetaxel monotherapy cycles. This suggests that docetaxel for metastatic prostate cancer can be administrated safely without prednisone from a pharmacological perspective.
Clinical trial identification
EudraCT: 2016-001269-10; Dutch trial register: NTR6037.
Legal entity responsible for the study
Erasmus MC Cancer Institute.
Funding
Dutch Uro-Oncology Studygroup.
Editorial Acknowledgement
Disclosure
R.J. van Soest: Honoraria: Astellas, Sanofi, Janssen. R. de Wit: Consultancy role, speakers fee: Sanofi. R.H.J. Mathijssen: Research support: Astellas, Bayer, Boehringer Ingelheim, Cristal Therapeutics, Novartis, Pamgene, Pfizer, Roche en Sanofi; Consultation fees: Novartis, Servier; Travel support: Astellas, Pfizer. All other authors have declared no conflicts of interest.
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