Cortisol as Biomarker for CYP17-Inhibition is Associated with Therapy Outcome of Abiraterone Acetate

Background Abiraterone acetate is an irreversible 17α-hydroxylase/C17, 20-lyase (CYP17) inhibitor approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. Inhibition of this enzyme leads to low testosterone and cortisol levels in blood. There is growing evidenc...

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Bibliographic Details
Published in:Pharmaceutical research 2023-12, Vol.40 (12), p.3001-3010
Main Authors: Bruin, Maaike A. C., Mohmaed Ali, Ma Ida, van Nuland, Merel, Jacobs, Bart A. W., Lucas, Luc, Dezentje, Vincent O., de Feijter, Jeantine M., Rosing, Hilde, Bergman, Andries M., Beijnen, Jos H., Huitema, Alwin D. R.
Format: Article
Language:English
Subjects:
Abiraterone Acetate - therapeutic use
Acetates
Acetic acid
Analysis
Biochemistry
Biomarkers
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Blood levels
Cancer patients
Care and treatment
Castration
Chromatography, Liquid
Corticosteroids
Cortisol
Enzymes
Hormones
Humans
Hydrocortisone
Liquid chromatography
Male
Mass spectrometry
Mass spectroscopy
Medical Law
Metastases
Metastasis
Original Research Article
Patients
Pharmacology/Toxicology
Pharmacy
Prostate cancer
Prostate-specific antigen
Prostate-Specific Antigen - therapeutic use
Prostatic Neoplasms, Castration-Resistant - drug therapy
Steroid 17-alpha-Hydroxylase
Survival
Tandem Mass Spectrometry
Testosterone
Testosterone - therapeutic use
Treatment Outcome
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Summary:Background Abiraterone acetate is an irreversible 17α-hydroxylase/C17, 20-lyase (CYP17) inhibitor approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. Inhibition of this enzyme leads to low testosterone and cortisol levels in blood. There is growing evidence that clinical efficacy of abiraterone is related to the rate of suppression of serum testosterone. However, quantification of very low levels of circulating testosterone is challenging. We therefore aimed to investigate whether circulating cortisol levels could be used as a surrogate biomarker for CYP17 inhibition in patients with mCRPC treated with abiraterone acetate. Patients and methods mCRPC patients treated with abiraterone acetate were included. Abiraterone and cortisol levels were measured with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). On treatment cortisol and abiraterone concentrations were related to treatment response and progression free survival. Results In total 117 patients were included with a median cortisol concentration of 1.13 ng/ml (range: 0.03 – 82.2) and median abiraterone trough concentration (C min ) of 10.2 ng/ml (range: 0.58 – 92.1). In the survival analyses, abiraterone C min  ≥ 8.4 ng/mL and cortisol  
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-023-03615-9