Development of strategic pharmaceutical therapy to improve QOL by suppressing brain metastasis and reducing side effects in lung cancer patients
| Project/Area Number |
17K08416
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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 |
Medical pharmacy
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
杉山 正 岐阜薬科大学, 薬学部, 教授 (30453054)
轟木 堅一郎 静岡県立大学, 薬学部, 教授 (70341451)
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| Project Period (FY) |
2017-04-01 – 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | afatinib / 臨床薬物動態 / 遺伝子多型 / 血漿中濃度 / トランスポーター / ABCG2 / 非小細胞肺癌 / 個別化医療 / 薬物動態 / 非小細胞肺がん / EGFR-TKI / 脳転移 |
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| Outline of Final Research Achievements |
A detailed information of afatinib, a non-small cell lung cancer drug, on its efficacy, safety and clinical pharmacokinetics in Japanese patients has not been revealed. In this study, a significant correlation was found between afatinib plasma levels and diarrhea severity. In addition, we analyzed genetic polymorphisms that might affect pharmacokinetics, and suggested that ABCG2 C421A might affect afatinib plasma levels and diarrhea severity.
Furthermore, we analyzed the pharmacokinetics in patients with carcinomatous meningitis. The prognosis was good in patients with high rates of afatinib transfer into the cerebrospinal fluid. However, in patients with low cerebrospinal fluid transfer rate, prognosis was poor and active drug treatment had to be abandoned.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、これまで情報の少なかった臨床におけるafatinib血漿中濃度と副作用重症度の関連および薬物動態関連遺伝子多型による副作用への影響を解析した。また、これまでにほとんど報告が無かった癌性髄膜炎併発症例でのafatinibの中枢移行動態を解析した。今後はさらに症例数を蓄積していくことでより明確なエビデンスが構築され、非小細胞肺癌における分子標的治療薬の個別化薬物療法の実現が可能になるものと期待でき、患者のQOLの向上と副作用を回避して薬物治療を継続することによる生存期間の延長も期待できる。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Effects of Pharmacokinetics-related Genetic Polymorphisms on the Side Effect Profile of Afatinib in Patients with Non-Small Cell Lung Cancer.2019
Author(s)
43.Hayashi H., Iihara H., Hirose C., Fukuda Y., Kitahora M., Kaito D., Yanase K., Endo J., Ohno Y., Suzuki A., Sugiyama T.
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Journal Title
Lung Cancer
Volume: 134
Pages: 1-6
DOI
Related Report
Peer Reviewed
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[Presentation] Relationship between severity of adverse events of afatinib and its pharmacokinetics and pharmacogenomics for EGFR mutation-positive non-small cell lung cancer2019
Author(s)
Gomyo T, Iihara H, Hayashi H, Endo J, Ito F, Yanase K, Kaito D, Sasaki Y, Sakai C, Hirose C, Fukuda Y, Sugiyama T, Suzuki A, Ohno Y
Organizer
American Thoracic Society International Conference 2019
Related Report
Int'l Joint Research
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[Presentation] 非小細胞肺癌治療薬アファチニブの抗腫瘍効果と副作用重症度に対する血漿中濃度と関連遺伝子多型の影響2019
Author(s)
上森 将吾, 林 秀樹, 飯原 大稔, 福田 純久, 廣瀬 智恵美, 北洞 美佳, 垣内 大蔵, 柳瀬 恒明, 遠渡 純輝, 大野 康, 鈴木 昭夫, 杉山 正
Organizer
第4回日本臨床薬理学会 東海・北陸地方会
Related Report
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[Presentation] アファチニブの抗腫瘍効果と副作用に対する血漿中濃度と動態関連遺伝子多型の影響2019
Author(s)
林 秀樹, 飯原 大稔, 廣瀬 智恵美, 福田 純久, 上森 将吾, 北洞 美佳, 垣内 大蔵, 柳瀬 恒明, 遠渡 純輝, 大野 康, 鈴木 昭夫, 杉山 正
Organizer
第57回日本癌治療学会学術集会
Related Report
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