Personalized dosing of targeted anticancer drugs by elucidating mechanisms underlying the variability in pharmacokinetics and pharmacodynamics

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K08902
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Asahikawa Medical College
• Principal Investigator: Fukudo Masahide 旭川医科大学, 医学部, 准教授 (60437233)
• Project Period (FY): 2016-04-01 – 2020-03-31
• 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

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.

Free Research Field

臨床薬理学

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。