A sub-pharmacological test dose does not predict individual docetaxel exposure in prostate cancer patients.
Publication year
2024Source
Cancer Chemotherapy and Pharmacology, 94, 3, (2024), pp. 437-441ISSN
Annotation
01 september 2024
Publication type
Article / Letter to editor
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Organization
Medical Oncology
Pharmacy
Journal title
Cancer Chemotherapy and Pharmacology
Volume
vol. 94
Issue
iss. 3
Page start
p. 437
Page end
p. 441
Subject
Medical Oncology - Radboud University Medical Center; Pharmacy - Radboud University Medical CenterAbstract
PURPOSE: Docetaxel is a cytotoxic drug used for first-line treatment of various malignancies. It has a narrow therapeutic index and shows wide interpatient variability in clearance and toxicity. Tools for individual dose optimization are needed to maximize efficacy and avoid toxicity. METHODS: We performed a proof-of-concept study (EudraCT 2016-003785-77) to evaluate whether pharmacokinetics after a sub-pharmacological test dose of 1000 µg docetaxel (millidose) could be used to predict therapeutic dose exposure. Thirty prostate cancer patients eligible for treatment with docetaxel as part of routine clinical care were included. An intravenous docetaxel millidose was administered 1-7 days prior to therapeutic docetaxel. After both doses plasma docetaxel concentrations were measured by ultra- high performance liquid chromatography-tandem mass spectrometry. The docetaxel clearance was estimated with non-linear mixed effects modeling. RESULTS: Geometric mean docetaxel clearance was 57.9 L/h (GCV 78.6%) after admission of a millidose and 40.3 L/h (GCV 60.7%) after admission of a therapeutic dose. The millidose and therapeutic dose in a single patient were not significantly correlated (Spearman's rho R = 0.02, P = 0.92). CONCLUSION: Docetaxel pharmacokinetics at milli- and therapeutic dose level showed insufficient correlation for individual dose optimization. However, the clearance of a docetaxel millidose and full dose are within the same order of magnitude. Therefore, docetaxel millidose pharmacokinetics could potentially facilitate prediction of docetaxel pharmacokinetics at a population level in situations where therapeutic dose levels are impractical, such as pharmacokinetic drug-drug interaction studies or pediatric studies.
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- Academic publications [244001]
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- Faculty of Medical Sciences [92816]
- Open Access publications [105058]
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