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4β‐hydroxycholesterol as an endogenous CYP3A marker in cancer patients treated with taxanes
Author(s) -
Graan AnneJoy M.,
Sparreboom Alex,
Bruijn Peter,
Jonge Evert,
Holt Bronno,
Wiemer Erik A. C.,
Verweij Jaap,
Mathijssen Ron H. J.,
Schaik Ron H. N.
Publication year - 2015
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12707
Subject(s) - endogeny , cancer , medicine , oncology , pharmacology
Aim 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. Methods Serum 4β‐OHC and cholesterol concentrations were determined in 291 paclitaxel and 151 docetaxel‐treated patients, and were subsequently correlated with taxane clearance. Results 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 ( r = 0.35 P = 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 ( r = 0.76, P = 0.03, 95% CI 0.12, 0.95). Conclusion 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.