Association of pharmacokinetics or pharmacogenomics with toxicity of erlotinib in patients with advanced non-small cell lung cancer
| Project/Area Number |
23590648
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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 |
Applied pharmacology
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| Research Institution | Tokyo National Hospital (Clinical research) (2013)
Showa University (2011-2012) |
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Principal Investigator |
HIROSE Takashi 独立行政法人国立病院機構東京病院(臨床研究部), その他部局等, その他 (40307038)
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| Co-Investigator(Kenkyū-buntansha) |
藤田 健一 昭和大学, 腫瘍分子生物学研究所, 准教授 (60281820)
佐々木 康綱 昭和大学, 医学部, 教授 (20235279)
大森 亨 昭和大学, 腫瘍分子生物学研究所, 准教授 (10276529)
山岡 利光 昭和大学, 腫瘍分子生物学研究所, 講師 (40384359)
足立 満 昭和大学, 医学部, 教授 (10095870)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ファーマコゲノミクス |
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| Research Abstract |
The orally administered erlotinib showed large interindividual variability in its pharmacokinetics. The aim of this study was to evaluate the association of pharmacokinetics or pharmacogenomics with toxicity of erlotinib in patients with advanced NSCLC. Plasma concentration of erlotinib was analyzed by high-performance liquid chromatography. The genotypes of ABCG2, ABCB1, ABCC2, CYP3A4, CYP3A5, CYP1A1, and CYP1A2 were analyzed by direct sequencing.
There were no statistically significant association of pharmacokinetics or pharmacogenomics with toxicity, such as skin toxicity, diarrhea, stomatitis, liver injury, and interstitial lung disease (ILD) of erlotinib. However, one patient died of drug induced ILD was homozygous for ABCG2 C>A and showed the highest AUC. Additionally, Cmax was trend toward to higher in 4 patients with liver injury than those without (p=0.054). In conclusion, the homozygote of ABCG2 C>A could be associated with elevated erlotinib exposure and drug-induced ILD.
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Report
(4 results)
Research Products
(4 results)
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[Presentation] 非小細胞肺癌に対するエルロチニブの毒性に影響を与える薬物動態、薬理遺伝学的検討
Author(s)
廣瀬敬, 藤田健一, 楠本壮二郎, 白井崇生, 村田泰則, 大木康成, 杉山智英, 石田博雄, 中嶌賢尚, 山岡利光, 奥田健太郎, 大西司, 大森亨, 佐々木康綱, 田村厚久, 大田健
Organizer
第54回日本呼吸器学会
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