Effects of prednisone on docetaxel pharmacokinetics in men with metastatic prostate cancer: A randomized drug-drug interaction study.
Br J Clin Pharmacol
; 85(5): 986-992, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30737835
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Prednisona
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Protocolos de Quimioterapia Combinada Antineoplásica
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Neoplasias de Próstata Resistentes à Castração
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Indutores do Citocromo P-450 CYP3A
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Docetaxel
Tipo de estudo:
Clinical_trials
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article