4β‐hydroxycholesterol as an endogenous CYP3A marker in cancer patients treated with taxanes. (12th August 2015)

• Record Type: Journal Article
• Authors: de Graan, Anne‐Joy M.; Sparreboom, Alex; de Bruijn, Peter; de Jonge, Evert; van der Holt, Bronno; Wiemer, Erik A. C.; Verweij, Jaap; Mathijssen, Ron H. J.; van Schaik, Ron H. N.
• Is Part Of: British journal of clinical pharmacology. Volume 80:Number 3(2015:Sep.)
• Page Start: 560
• Page End: 568
• Publication Date: 2015-08-12
• Subjects: Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.12707
• Languages: English
• ISSNs: 0306-5251

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bcp12707-sec-0001" sec-type="section"> <title>Aim</title> <p>Taxanes are anti‐cancer agents used to treat several types of solid tumours. They are metabolized by cytochrome P450 (CYP) 3A, displaying a large pharmacokinetic (PK) variability. In this study, we evaluated the endogenous CYP3A4 marker 4β‐hydroxycholesterol (4β‐OHC) as a potential individual taxane PK predictor.</p> </sec> <sec id="bcp12707-sec-0002" sec-type="section"> <title>Methods</title> <p>Serum 4β‐OHC and cholesterol concentrations were determined in 291 paclitaxel and 151 docetaxel‐treated patients, and were subsequently correlated with taxane clearance.</p> </sec> <sec id="bcp12707-sec-0003" sec-type="section"> <title>Results</title> <p>In the patients treated with paclitaxel, no clinically relevant correlations between the 4β‐OHC or 4β‐OHC : cholesterol ratio and paclitaxel clearance were found. In the patients treated with docetaxel, 4β‐OHC concentration was weakly correlated with docetaxel clearance in males (<italic>r</italic> = 0.35 <italic>P</italic> = 0.01, 95% CI 0.08, 0.58). Of the 10% patients with taxane outlier clearance values, 4β‐OHC did correlate with docetaxel clearance in males (<italic>r</italic> = 0.76, <italic>P</italic> = 0.03, 95% CI 0.12, 0.95).</p> </sec> <sec id="bcp12707-sec-0004" sec-type="section"> <title>Conclusion</title> <p>There was no clinical correlation between paclitaxel clearance and the CYP3A4 activity markers 4β‐OHC or the 4β‐OHC : cholesterol ratio. A weak correlation was observed between 4β‐OHC and docetaxel clearance, but only in males. This endogenous CYP3A4 marker has limited predictive value for taxane clearance in patients.</p> </sec> </abstract>