Therapeutic drug monitoring of EGFR-KIs for non-small cell lung cancer patients

Research Project

Project/Area Number	16K09568
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Respiratory organ internal medicine
Research Institution	Shizuoka Cancer Center Research Institute
Principal Investigator	Hirotsugu Kenmotsu 静岡県立静岡がんセンター(研究所), その他部局等, 研究員 (50602637)
Co-Investigator(Kenkyū-buntansha)	今村知世慶應義塾大学, 医学部(信濃町), 講師 (00570954) 谷川原祐介慶應義塾大学, 医学部(信濃町), 教授 (30179832)
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	非小細胞肺癌 / 臨床薬理学 / EGFRチロシンキナーゼ阻害剤 / 癌 / 薬理学
Outline of Final Research Achievements	Seventy non-small cell lung cancer (NSCLC) patients were included in this study. Response was not associated with the area under the concentration-time curve (AUC). There was also no significant difference in progression-free survival between patients with AUC > 37.0 μg・h/mL and <= 37.0 μg・h/mL. Ctrough was significantly correlated with the grade of skin rash (p<0.01), but not with objective response. The lack of a relationship between erlotinib exposure and efficacy shows that the approved dose of erlotinib is sufficient to reach the therapeutic range in NSCLC patients, even with dose reduction due to toxicities.
Academic Significance and Societal Importance of the Research Achievements	本課題で行われた3つの臨床試験の結果より、EGFR遺伝子変異陽性の非小細胞肺癌において、EGFRチロシンキナーゼ阻害剤の血液中濃度とその治療効果（奏効割合、無増悪生存期間）には相関は認めなかった。一方で、副作用と血中濃度には相関を認め、副作用を減らすために薬剤の用量を調整することの有用性についてはさらに検討が必要であると考えられた。チロシンキナーゼ阻害剤はEGFR 遺伝子変異陽性の非小細胞肺がん患者に対するキードラッグであり、今後も個別化投与の確立を目指すことが重要である。