Personalized dosing of targeted anticancer drugs by elucidating mechanisms underlying the variability in pharmacokinetics and pharmacodynamics
| Project/Area Number |
16K08902
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | がん分子標的薬 / 薬物動態 / 代謝物 / 薬剤感受性 / 個別化投与設計 / 代謝 / Precision Medicine / 薬物代謝酵素 / トランスポーター |
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| Outline of Final Research Achievements |
We demonstrated that severity of hand-foot skin reaction induced by regorafenib was significantly associated with sum of trough concentrations of regorafenib and its active metabolites M2/M-5. Furthermore, the cutoff value to predict the development of this adverse event (grade 2 or higher) appeared to be approximately 5 μg/mL. It was clarified that pharmacokinetically-guided dosing of pazopanib with therapeutic drug monitoring (TDM) significantly prolonged the duration of treatment with reduced toxicity, as compared with the historical control group.
These findings suggest that TDM could be a useful tool to optimize targeted anticancer therapies by avoiding early discontinuation due to intolerable toxicity.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、レゴラフェニブやパゾパニブをはじめとするがん分子標的薬の臨床薬物動態を把握する上で有用な知見を提供するものであり、特にTDMを利用した個別化処方設計支援に基づく治療アウトカムの改善が期待され、がん分子標的薬の適正使用の推進とそれによる医療費の抑制にも貢献することが考えられる。
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Report
(5 results)
Research Products
(19 results)
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[Journal Article] Lymph Node Metastasis From Gastroesophageal Cancer Successfully Treated by Nivolumab: A Case Report of a Young Patient.2019
Author(s)
Kashima S, Tanabe H, Tanino M, Kobayashi Y, Murakami Y, Iwama T, Sasaki T, Kunogi T, Takahashi K, Ando K, Ueno N, Moriichi K, Fukudo M, Tasaki Y, Hosokawa M, Mizukami Y, Fujiya M, Okumura T.
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Journal Title
Front Oncol.
Volume: 9
Pages: 1375-1375
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pharmacokinetics and pharmacodynamics of once-daily tacrolimus compared with twice-daily tacrolimus in the early stage after living donor liver transplantation2018
Author(s)
Iwasaki M, Yano I, Fukatsu S, Hashi S, Yamamoto Y, Sugimoto M, Fukudo M, Masuda S, Nakagawa S, Yonezawa A, Kaido T, Uemoto S, Matsubara K
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Journal Title
Therapeutic Drug Monitoring
Volume: 印刷中
NAID
Related Report
Peer Reviewed
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[Presentation] Regorafenib pharmacokinetics and exposure-toxicity relationship in Japanese cancer patients2018
Author(s)
Fukudo M, Kubo Y, Shinden Y, Koeda M, Tani C, Miyamoto M, Asai K, Furukawa H, Ueno N, Okumura T, Tasaki Y
Organizer
第16回国際TDM会議 (IATDMCT2018)
Related Report
Int'l Joint Research
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