論文

査読有り
2015年8月

Assessment of Sunitinib-Induced Toxicities and Clinical Outcomes Based on Therapeutic Drug Monitoring of Sunitinib for Patients With Renal Cell Carcinoma

CLINICAL GENITOURINARY CANCER
  • Satoshi Noda
  • ,
  • Takashi Otsuji
  • ,
  • Masato Baba
  • ,
  • Tetsuya Yoshida
  • ,
  • Susumu Kageyama
  • ,
  • Keisei Okamoto
  • ,
  • Yusaku Okada
  • ,
  • Akihiro Kawauchi
  • ,
  • Hiroyuki Onishi
  • ,
  • Daiki Hira
  • ,
  • Shin-ya Morita
  • ,
  • Tomohiro Terada

13
4
開始ページ
350
終了ページ
358
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.clgc.2015.01.007
出版者・発行元
CIG MEDIA GROUP, LP

The benefit of pharmacokinetic assessment of sunitinib remains unknown. We reported that patients with total sunitinib (sunitinib + its active metabolite SU12662) >= 100 ng/mL showed high incidence of Grade >= 3 toxicities and worsening clinical outcomes. Thus, pharmacokinetic assessment of sunitinib could be helpful for dose optimization.
Background: Sunitinib has been approved for the treatment of metastatic renal cell carcinoma (RCC). Sunitinib pharmacokinetics shows a large interpatient variability. Patients and Methods: A retrospective, observational clinical study of 21 patients with RCC was performed. Sunitinib was administered for 4 weeks of a 6-week cycle for the first cycle. We evaluated the association of sunitinib-induced toxicities and clinical outcomes with the trough total sunitinib concentration in a steady state during the first cycle. Results: The median total sunitinib concentration was 91.8 ng/mL (range, 49.8-205 ng/mL). There was an association between total sunitinib concentration and the severity of thrombocytopenia, anorexia, and fatigue. Patients with >= 100 ng/mL total sunitinib (n = 8), compared with patients with < 100 ng/mL (n = 13), had a greater incidence of Grade >= 3 toxicities (6 patients [75.0%] vs. 3 patients [23.1%]). Patients with < 100 ng/mL total sunitinib had significantly longer time to treatment failure (TTF) and progression-free survival (PFS) time than patients with >= 100 ng/mL (median TTF, 590 vs. 71 days; P = .04; median PFS, 748 vs. 238 days; P = .02). Conclusion: Results of this study suggest that therapeutic drug monitoring of sunitinib could be useful for avoiding severe toxicities. Dose reduction might be needed, especially when the total sunitinib concentration is >= 100 ng/mL, to avoid unnecessary early discontinuation of treatment.

Web of Science ® 被引用回数 : 28

リンク情報
DOI
https://doi.org/10.1016/j.clgc.2015.01.007
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25701374
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000357880000036&DestApp=WOS_CPL

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