Influence of Enzalutamide on Cabazitaxel Pharmacokinetics: a Drug-Drug Interaction Study in Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients.
Autor: | Belderbos BPS; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Bins S; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., van Leeuwen RWF; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands., Oomen-de Hoop E; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., van der Meer N; Clinical Trial Center, 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., Overkleeft ENM; Department of Internal Medicine, Ikazia Hospital, Rotterdam, the Netherlands., van der Deure WM; Department of Internal Medicine, Groene Hart Hospital, Gouda, 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., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. a.mathijssen@erasmusmc.nl. |
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Jazyk: | angličtina |
Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2018 Feb 01; Vol. 24 (3), pp. 541-546. Date of Electronic Publication: 2017 Nov 17. |
DOI: | 10.1158/1078-0432.CCR-17-2336 |
Abstrakt: | Purpose: In ongoing clinical research on metastatic castration-resistant prostate cancer (mCRPC) treatment, the potential enhanced efficacy of the combination of taxanes with AR-targeted agents, that is, enzalutamide and abiraterone, is currently being explored. Because enzalutamide induces the CYP3A4 enzyme and taxanes are metabolized by this enzyme, a potential drug-drug interaction needs to be investigated. Experimental Design: Therefore, we performed a pharmacokinetic cross-over study in mCRPC patients who were scheduled for treatment with cabazitaxel Q3W (25 mg/m 2 ). Patients were studied for three consecutive cabazitaxel cycles. Enzalutamide (160 mg once daily) was administered concomitantly after the first cabazitaxel cycle, during 6 weeks. Primary endpoint was the difference in mean area under the curve (AUC) between the first (cabazitaxel monotherapy) and third cabazitaxel cycle, when enzalutamide was added. Results: A potential clinically relevant 22% (95% CI, 9%-34%; P = 0.005) reduction in cabazitaxel exposure was found with concomitant enzalutamide use. The geometric mean AUC (©2017 American Association for Cancer Research.) |
Databáze: | MEDLINE |
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