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Associations among regorafenib concentrations, severe adverse reactions, and ABCG2 and OATP1B1 polymorphisms

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Abstract

Purpose

The ability of predicting severe adverse reactions caused by regorafenib is important. We evaluated regorafenib concentrations for adverse reaction risks and assessed the relevance of laboratory values and gene polymorphisms.

Methods

A total of 28 Japanese cancer patients who were treated with regorafenib were evaluated for the steady state of serum regorafenib concentrations and adverse reactions for 28 days. In addition, we determined the association of regorafenib concentrations with ABCG2 and OATP1B1 polymorphisms, which are regorafenib transporters.

Results

Regorafenib concentrations were significantly higher in the group with Grade 2 or higher total bilirubin elevation and thrombocytopenia compared with the group with grades 0 or 1 [3.45 (2.18–7.31) vs. 1.76 (0.26–2.77) µg/mL, P = 0.01 and 3.45 (2.12–7.31) vs. 1.76 (0.26–2.77) µg/mL, P = 0.02, respectively]. A strong association was noted between serum regorafenib concentrations and total bilirubin levels, but the physical and genetic factors predicting regorafenib pharmacokinetics could not be clarified.

Conclusions

Regorafenib concentrations were associated with total bilirubin elevation and thrombocytopenia. Total serum bilirubin could be a useful marker when estimating regorafenib pharmacokinetics.

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Authors and Affiliations

  1. Department of Pharmacy, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan

    Akimitsu Maeda, Ayako Hasegawa, Kazuhide Inaguma & Masaki Kajita

  2. Department of Pharmacy, Kobe City Hospital Organization, Kobe City Medical Center General Hospital, Kobe, Japan

    Kei Irie

  3. Department of Pharmaceutics, Faculty of Pharmaceutical Science, Kobe Gakuin University, Kobe, Japan

    Kei Irie & Shoji Fukushima

  4. Department of Cellular and Molecular Function Analysis, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan

    Hitoshi Ando

  5. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

    Hiroya Taniguchi, Shigenori Kadowaki & Kei Muro

  6. Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan

    Masahiro Tajika

  7. Division of Molecular Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan

    Masahiro Aoki

  8. Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke, Japan

    Akio Fujimura

Authors
  1. Akimitsu Maeda
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  2. Kei Irie
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  3. Hitoshi Ando
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  8. Masahiro Tajika
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  9. Masahiro Aoki
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  10. Kazuhide Inaguma
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  11. Masaki Kajita
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  13. Shoji Fukushima
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Corresponding author

Correspondence to Akimitsu Maeda.

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Maeda, A., Irie, K., Ando, H. et al. Associations among regorafenib concentrations, severe adverse reactions, and ABCG2 and OATP1B1 polymorphisms. Cancer Chemother Pharmacol 83, 107–113 (2019). https://doi.org/10.1007/s00280-018-3710-9

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  • DOI: https://doi.org/10.1007/s00280-018-3710-9

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