Cancer Chemotherapy and Pharmacology

, Volume 83, Issue 1, pp 107–113 | Cite as

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

  • Akimitsu MaedaEmail author
  • Kei Irie
  • Hitoshi Ando
  • Ayako Hasegawa
  • Hiroya Taniguchi
  • Shigenori Kadowaki
  • Kei Muro
  • Masahiro Tajika
  • Masahiro Aoki
  • Kazuhide Inaguma
  • Masaki Kajita
  • Akio Fujimura
  • Shoji Fukushima
Original Article



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.


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.


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.


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


Adverse reactions Bilirubin Pharmacokinetics Regorafenib OATP1B1 SLCO1B1 


Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Akimitsu Maeda
    • 1
    Email author
  • Kei Irie
    • 2
    • 3
  • Hitoshi Ando
    • 4
  • Ayako Hasegawa
    • 1
  • Hiroya Taniguchi
    • 5
  • Shigenori Kadowaki
    • 5
  • Kei Muro
    • 5
  • Masahiro Tajika
    • 6
  • Masahiro Aoki
    • 7
  • Kazuhide Inaguma
    • 1
  • Masaki Kajita
    • 1
  • Akio Fujimura
    • 8
  • Shoji Fukushima
    • 3
  1. 1.Department of PharmacyAichi Cancer Center HospitalNagoyaJapan
  2. 2.Department of PharmacyKobe City Hospital Organization, Kobe City Medical Center General HospitalKobeJapan
  3. 3.Department of Pharmaceutics, Faculty of Pharmaceutical ScienceKobe Gakuin UniversityKobeJapan
  4. 4.Department of Cellular and Molecular Function AnalysisKanazawa University Graduate School of Medical SciencesKanazawaJapan
  5. 5.Department of Clinical OncologyAichi Cancer Center HospitalNagoyaJapan
  6. 6.Department of EndoscopyAichi Cancer Center HospitalNagoyaJapan
  7. 7.Division of Molecular PathologyAichi Cancer Center Research InstituteNagoyaJapan
  8. 8.Division of Clinical Pharmacology, Department of PharmacologyJichi Medical UniversityShimotsukeJapan

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