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Comparison of docetaxel pharmacokinetics between castration-resistant and hormone-sensitive metastatic prostate cancer patients.
Vermunt, Marit A C; van Nuland, Merel; van der Heijden, Lisa T; Rosing, Hilde; Beijnen, Jos H; Bergman, Andries M.
Afiliação
  • Vermunt MAC; Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands. m.vermunt@nki.nl.
  • van Nuland M; Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.
  • van der Heijden LT; Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.
  • Rosing H; Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.
  • Beijnen JH; Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands.
  • Bergman AM; Department of Pharmaceutical Sciences, Utrecht University, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands.
Cancer Chemother Pharmacol ; 89(6): 785-793, 2022 06.
Article em En | MEDLINE | ID: mdl-35467095
PURPOSE: Recently, docetaxel treatment of metastatic prostate cancer patients shifted towards the hormone-sensitive stage of the disease. There are contradictive reports on differences in toxicity of docetaxel in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) patients. Possible differences in toxicity might be attributed to different pharmacokinetics (PK) in the two patient populations. METHODS: Patients with mCRPC or mHSPC and a standard indication for docetaxel treatment were included in the study. All patients had suppressed serum testosterone levels (≤ 0.5 ng/mL or 1.73 nmol/L). Venous blood samples were obtained at the first docetaxel treatment, until 48 h after infusion. Plasma concentrations of docetaxel, unbound docetaxel and docetaxel metabolites were measured using validated liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) assays and compared between the two groups. Moreover, serum levels of docetaxel transporting α1-acid glycoprotein were measured and docetaxel toxicity recorded. RESULTS: A total of ten mCRPC and nine mHSPC patients were included in the study. The two cohorts differed in the number of prior treatments and opiate use, which were higher for mCRPC patients. The docetaxel PK was not different between mCRPC and mHSPC patients, with areas under the plasma concentration versus time curve (AUC0-48) 1710 [coefficient of variation (CV) 28.4%] and 1486 (CV 25.2%) ng/mL*h (p = 0.27), respectively. Also, the PK profile of unbound docetaxel, M1/M3, M2 and M4 metabolites were similar in both groups. Docetaxel doses were reduced in 50% of the mCRPC patients and 11% of the mHSPC patients. CONCLUSION: The PK profile of docetaxel was similar in mCPRC and mHSPC patients. Therefore, possible differences in toxicity between mCRPC and mHSPC patients cannot be explained by differences in docetaxel PK in our study population. These results suggest that treatment adaptations are not recommended in the new population of patients with mHSPC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Diagnostic_studies / Observational_studies Limite: Humans / Male Idioma: En Revista: Cancer Chemother Pharmacol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Diagnostic_studies / Observational_studies Limite: Humans / Male Idioma: En Revista: Cancer Chemother Pharmacol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Holanda