Effects of pharmacokinetics on the clinical outcomes of gefitinib treatment in patients with EGFR-mutation positive non-small cell lung cancer
| Project/Area Number |
17K09602
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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 |
Respiratory organ internal medicine
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| Research Institution | Akita University |
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Principal Investigator |
Sato Kazuhiro 秋田大学, 医学系研究科, 特任准教授 (30436191)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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)
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| Keywords | 個別化治療 / 肺癌 / 薬物動態 / 代謝酵素 / EGFR-TKI / 血中濃度 / トランスポーター / 遺伝子多型 / 非小細胞肺癌 / EGFR-TKI血中濃度 / 予後予測因子 / 分子標的治療 |
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| Outline of Final Research Achievements |
ABCG2 is thought to inhibit the activities of certain gefitinib transporters, thereby affecting drug pharmacokinetics. The C421A polymorphism affects the function and expression of ABCG2 on the cell membrane. We evaluated the plasma concentrations of gefitinib in patients with and without the ABCG2 C421A polymorphism. Plasma gefitinib concentration and ABCG2 C421A status were determined. The patients were divided into CC- and CA/AA genotype groups. We compared the trough and peak gefitinib levels and the AUC values for 24-h gefitinib concentrations. The mean trough gefitinib level and AUC value for 24-h gefitinib concentration were significantly lower in the CA/AA group compared to the CC group. Among patients taking PPIs, the mean trough gefitinib level was significantly lower in the CA/AA group than the CC group. The CA/AA-type of ABCG2 C421A polymorphism may be associated with lower gefitinib plasma concentrations.
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| Academic Significance and Societal Importance of the Research Achievements |
血中濃度を測定しターゲット濃度を継続させることで、1）副作用を未然に防止でき、2）無効域推移による無駄な時間とコストを削減でき、攻めの治療が実施できるはずである。本研究の特色は、TDMのみならず薬剤血中濃度を予測しうる遺伝子多型より、治療開始前から効果と有害事象を予測することある。それにより試行錯誤的治療を回避し、より早くターゲット血中濃度に到達させることで、効率良く治療を進めることができるようになる。本検討によってもたらされる治療戦略はいかに安全かつ効率的に治療を継続させるかであるが、そればかりか、高齢化社会を迎えるに当たり、高騰の一途をたどる薬剤費の抑制を図れる手段の一つともなりえる。
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Report
(6 results)
Research Products
(20 results)
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[Journal Article] Association Between Endothelial Progenitor Cells and Treatment Response in Non-Squamous Non-small Cell Lung Cancer Treated with Bevacizumab2017
Author(s)
KAZUHISA SUDO, KAZUHIRO SATO, SHO SAKAMOTO, YUKIYASU HASEGAWA, MARIKO ASANO, YUJI OKUDA, MASAHIDE TAKEDA, MASAAKI SANO, HIROYUKI WATANABE, TAKANOBU SHIOYA , HIROSHI ITO
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Journal Title
Anticancer Research
Volume: 37
Issue: 10
Pages: 5565-5571
DOI
Related Report
Peer Reviewed
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[Presentation] Association between proton-pump inhibitors and the ABCG2 C421A polymorphism and plasma concentration of gefitinib2021
Author(s)
Sakamoto,S.,Sato,K.,Goshima,S.,Asahi,R.,Takita,Y.,Omoto,E.,Izumiya,Y.,Kumagai,N.,Hasegawa,Y.,Yokota,H.,Okuda,Y.,Asano,M.,Akamine,Y.,Takeda,M.,Miura,M. and Nakayama,K.
Organizer
The 25th Congress of the Asian Pacific Society of Respirology
Related Report
Int'l Joint Research
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