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Relationships between sunitinib plasma concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma

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Abstract

Background

The aim was to investigate the relationships between total sunitinib plasma concentrations (sunitinib plus its active metabolite; N-desethyl sunitinib) and clinical outcomes in Japanese patients with metastatic renal cell carcinoma (mRCC).

Methods

Twenty patients with mRCC were enrolled following treatment with sunitinib. To assess safety, the total sunitinib concentration range up to discontinuation of treatment and dosage reduction associated with adverse events within 6 weeks from initiating administration were analyzed. The longest administered sunitinib dosage was defined as the maintenance dose, and the relationship between total sunitinib concentration at the maintenance dosage and sunitinib efficacy was investigated.

Results

Total sunitinib concentration was significantly higher in patients who discontinued treatment or had dosage reduction due to adverse events within 6 weeks after initiation of sunitinib than in patients who continued treatment with the initial dosage. The time to treatment failure, progression-free survival, and overall survival were better in patients with total sunitinib concentrations < 50 ng/mL than in those with concentrations ≥ 50 ng/mL.

Conclusions

The present study demonstrated that the effective range of total sunitinib concentration in Japanese patients with mRCC was lower than 50–100 ng/mL which was previously reported. These results indicate that therapeutic drug monitoring could maintain the therapeutic effect of sunitinib while minimizing adverse events by personalizing sunitinib dosages for Japanese patients with mRCC.

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Abbreviations

mRCC:

Metastatic renal cell carcinoma

TKI:

Tyrosine kinase inhibitor

VEGFR:

Vascular endothelial growth factor receptor

PDGFR:

Platelet-derived growth factor receptor

PFS:

Progression-free survival

TDM:

Therapeutic drug monitoring

PK:

Pharmacokinetics

PD:

Pharmacodynamics

LC-MS/MS:

Liquid chromatography ionization tandem mass spectrometry

TTF:

Time to treatment failure

ABCG2:

ATP-binding cassette sub-family G member 2

ABCB1:

ATP-binding cassette sub-family B member 1

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Acknowledgements

The authors would like to thank all of the patients and the expert urology nurses and the skillful pharmacists in Tohoku University Hospital who were involved in this study.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan

    Shinya Takasaki, Masafumi Kikuchi, Masaki Tanaka, Masato Suzuka, Aoi Noda, Yuji Sato, Hiroaki Yamaguchi & Nariyasu Mano

  2. Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan

    Yoshihide Kawasaki, Shinichi Yamashita, Koji Mitsuzuka, Akihiro Ito & Yoichi Arai

  3. Department of Urology, Sendai Medical Center, 2-6-8 Miyagino, Miyaginoku, Sendai, Miyagi, 893-8520, Japan

    Hideo Saito

Authors
  1. Shinya Takasaki
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  2. Yoshihide Kawasaki
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  3. Masafumi Kikuchi
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  4. Masaki Tanaka
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  5. Masato Suzuka
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  6. Aoi Noda
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  7. Yuji Sato
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  8. Shinichi Yamashita
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  11. Akihiro Ito
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  12. Hiroaki Yamaguchi
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  13. Yoichi Arai
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  14. Nariyasu Mano
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Corresponding author

Correspondence to Yoshihide Kawasaki.

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The authors declare that have no competing interests.

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Takasaki, S., Kawasaki, Y., Kikuchi, M. et al. Relationships between sunitinib plasma concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma. Int J Clin Oncol 23, 936–943 (2018). https://doi.org/10.1007/s10147-018-1302-7

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  • DOI: https://doi.org/10.1007/s10147-018-1302-7

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