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Impact of age on exposure to oral antiandrogen therapies in clinical practice

Prostate Cancer and Prostatic Diseases volume 22, pages 168–175 (2019)Cite this article

Subjects

Abstract

Background

Oral antiandrogen therapies are predominantly used in older men, but real-life studies evaluating the impact of age on pharmacokinetic exposure are lacking. This study aims to evaluate the impact of age on the pharmacokinetic profiles of abiraterone acetate and enzalutamide in clinical practice.

Patients and methods

Retrospective observational study to evaluate the impact of age on the first steady-state sample of patients treated with abiraterone acetate or enzalutamide in routine daily clinical practice. The effect of age on target attainment was assessed.

Results

For abiraterone acetate and enzalutamide, 71 and 64 patients were included, respectively. Baseline patients’ characteristics and administered doses were not age-dependent. No age-related differences were observed in exposure to the main metabolites of abiraterone acetate, except for active metabolite Δ(4)-Abiraterone (D4A) with a median plasma concentration of 2.5 × 10−3 mg/L in the oldest versus 1.3 × 10−3 mg/L in the youngest age quartile (coefficient of variation, CV, 72%, p = 0.03). For enzalutamide, no significant differences in exposure were found, except for carboxylic acid enzalutamide, having a median plasma concentration of 5.8 mg/L versus 3.9 mg/L in the oldest versus the youngest age quartile (CV 66%, p = 0.03). However, this was driven by one patient aged 99 years old. Age had no significant influence on target attainment of either compound.

Conclusions

This study showed no significant impact of age on the pharmacokinetic profiles of abiraterone acetate and enzalutamide, except for the active metabolite D4A and the inactive metabolite carboxylic acid enzalutamide, both having significantly higher exposure in older males. Target attainments of abiraterone and enzalutamide were not significantly affected by age, which suggests that age has no clinically relevant impact on exposure to these oral antiandrogen therapies. However, the clinical impact of higher exposure to D4A in older males remains undetermined.

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Author notes

  1. These authors have contributed equally and thus share first authorship: Marie-Rose B.S. Crombag, Merel van Nuland

Authors and Affiliations

  1. Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute and MC Slotervaart, Amsterdam, The Netherlands

    Marie-Rose B. S. Crombag, Merel van Nuland, Hilde Rosing, Alwin D. R. Huitema & Jos H. Beijnen

  2. Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Marie-Rose B. S. Crombag, Merel van Nuland, Jan H. M. Schellens, Alwin D. R. Huitema & Jos H. Beijnen

  3. Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Andries M. Bergman

  4. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Jan H. M. Schellens & Jos H. Beijnen

  5. Division of Medical Oncology, Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Jan H. M. Schellens

  6. Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    Alwin D. R. Huitema

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Correspondence to Marie-Rose B. S. Crombag.

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Crombag, MR.B.S., van Nuland, M., Bergman, A.M. et al. Impact of age on exposure to oral antiandrogen therapies in clinical practice. Prostate Cancer Prostatic Dis 22, 168–175 (2019). https://doi.org/10.1038/s41391-018-0096-z

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