Impact of trough abiraterone level on adverse events in patients with prostate cancer treated with abiraterone acetate

Yoshiko Takahashi, Shintaro Narita, Masaki Shiota, Masatomo Miura, Hideaki Kagaya, Soki Kashima, Ryohei Yamamoto, Taketoshi Nara, Mingguo Huang, Kazuyuki Numakura, Mitsuru Saito, Masatoshi Eto, Tomonori Habuchi

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: We assessed the impact of plasma trough concentrations of abiraterone (ABI) and its metabolite Δ4-abiraterone (D4A) and related polymorphisms on adverse events (AEs) in patients with metastatic prostate cancer who received abiraterone acetate (AA). Methods: This prospective study enrolled patients with advanced prostate cancer treated with AA between 2016 and 2021. Plasma trough concentrations of ABI and D4A were measured using high-performance liquid chromatography. The impact of HSD3B1 rs1047303, SRD5A2 rs523349, and cytochrome P450 family 3A member 4 rs2242480 polymorphisms on plasma concentrations of ABI and D4A and the incidence of AEs were also assessed. Results: In 68 patients treated with AA, the median ABI and D4A concentrations were 18.1 and 0.94 ng/mL, respectively. The high plasma trough concentration of ABI (≥ 20.6 ng/mL) was significantly associated with the presence of any AE and its independent risk factor based on multivariable analysis (odds ratio, 7.20; 95% confidence interval (CI): 2.20–23.49). Additionally, a high plasma trough concentration of ABI was an independent risk factor of time to withdraw AA (hazard ratio, 4.89; 95% CI: 1.66–14.38). The risk alleles of three polymorphisms were not statistically associated with the ABI and D4A concentrations and the incidence of AEs. Conclusions: The plasma trough concentration of ABI is associated with the presence of AEs and treatment failure after AA administration. ABI concentration monitoring may be useful in patients with prostate cancer who received AA.

Original languageEnglish
Pages (from-to)89-98
Number of pages10
JournalEuropean Journal of Clinical Pharmacology
Volume79
Issue number1
DOIs
Publication statusPublished - Jan 2023

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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