Development of the treatment strategy for molecular target anticancer drugs to avoid serious side effects

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07150
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Akita University
• Principal Investigator: MIURA MASATOMO 秋田大学, 医学系研究科, 教授 (30265194)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 分子標的治療薬 / 血中濃度 / 遺伝子多型 / バイオマーカー / 個別化治療

Outline of Final Research Achievements

There was no significant difference in the plasma concentration of ponatinib among genotypes of ABCB1 or ABCG2 421C>A transporters; however, patients with SNPs associated with low P-glycoprotein activity had significantly higher cerebrospinal fluid-to-plasma ratios of ponatinib. There were no significant differences in the osimertinib AUC between genotypes of CYP3A4/5 or ABC transporters. Furthermore, there were no significant differences in the osimertinib AUC between patients with diarrhea, skin rash, or hepatotoxicity and those without these conditions. In multivariate analysis, only serum albumin value was an independent factor predicting the osimertinib AUC. In patients with partial response and stable disease for lenvatinib therapy, angiopoietin-2 (Ang-2) at 1 month were significantly lower than Ang-2 at baseline. The change of Ang-2 at 1 month from baseline may be important as a biomarker of the inhibitory effect of angiogenesis by lenvatinib.

Free Research Field

臨床薬理学

Academic Significance and Societal Importance of the Research Achievements

日本人にとって添付文書記載の投与量は高用量であることが多く、治療開始早期で治療継続が困難となるケースが散見される。分子標的治療薬の効果や副作用は血中濃度と相関することが知られているため、治療開始後早期に血中濃度を測定し投与量を調節することで、重篤な副作用の回避、支持療法による医薬品使用の回避、さらに高額な医薬品費抑制に繋がる。血中濃度や遺伝子多型解析による個別化は患者に利益をもたらすと考えられる。