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

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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.

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Acknowledgements

The authors wish to express their appreciation to Yukiko Sugiyama, Nana Tomatsu, Yoko Mitobe, Ken Watanabe, Shihoko Nishikawa, Noriko Hakoda, and Eriko Gunshima for their support.

Funding

This study was supported in part by the research grant from the Nakatomi Foundation and the MEXT/JSPS (Kakenhi, No. 19K09663, 21K06592, 19K18551, 19K16706, 21H03064).

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Authors and Affiliations

  1. Department of Urology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan

    Yoshiko Takahashi, Shintaro Narita, Soki Kashima, Ryohei Yamamoto, Taketoshi Nara, Mingguo Huang, Kazuyuki Numakura, Mitsuru Saito & Tomonori Habuchi

  2. Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Masaki Shiota & Masatoshi Eto

  3. Department of Pharmacy, Akita University Hospital, Akita, Japan

    Masatomo Miura & Hideaki Kagaya

Authors
  1. Yoshiko Takahashi
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  2. Shintaro Narita
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  4. Masatomo Miura
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Contributions

All authors contributed to the design of the study or assisted with the data analysis/interpretation of the data, or both. All authors assisted in the preparation of the manuscript, reviewed the manuscript, and provided their approval for submission. All authors agree to be accountable for all aspects of the work presented.

Corresponding author

Correspondence to Shintaro Narita.

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Competing interests

This study was supported in part by the research grant from the Nakatomi Foundation and the MEXT/JSPS (Kakenhi, No. 19K09663, 21K06592, 19K18551, 19K16706, 21H03064).

Ethics approval

The study protocol was conducted in accordance with the Declaration of Helsinki. The protocol was approved by the Independent Ethics Committee.

Consent to participate

All patients provided written informed consent prior to undergoing any study-specific procedure.

Consent for publication

Not applicable.

Conflict of interest

Shintaro Narita received honoraria from Janssen Pharmaceutical K.K. Masaaki Shiota received honoraria from Janssen Pharmaceutical K.K., AstraZeneca K.K., and Astellas Pharma Inc.; and research funding support from Daiichi Sankyo Company. Tomonori Habuchi also received honoraria from Janssen Pharmaceutical K.K.; Takeda Pharmaceutical Company Ltd.; Astellas Pharma Inc.; Daiichi Sankyo Company, Ltd.; AstraZeneca K.K.; Sanofi S.A.; and Bayer AG. Tomonori Habuchi also received research funding support from Mochida Pharmaceutical Co. The other authors have no disclosures.

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Takahashi, Y., Narita, S., Shiota, M. et al. Impact of trough abiraterone level on adverse events in patients with prostate cancer treated with abiraterone acetate. Eur J Clin Pharmacol 79, 89–98 (2023). https://doi.org/10.1007/s00228-022-03420-0

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