Development of personalized chemotherapy with novel molecular targeted agents based on pharmacokinetic and pharmacogenomic analysis

• Project/Area Number: 21790520
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Applied pharmacology
• Research Institution: Kyoto University
• Principal Investigator: FUKUDO Masahide Kyoto University, 医学研究科, 助教 (60437233)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 分子標的治療薬 / 薬物動態 / 副作用 / ゲノム情報 / 個別化投与設計

Research Abstract

We examined the relationships between pharmacokinetics and genetic polymorphsims as well as adverse events in patients treated with molecular targeted anticancer agents. The genetic variation (421C>A) of ABCG2, an efflux transporter, was related to increased sunitinib exposure, resulting in the development of side effects. Furthermore, erlotinib-related rash was closely associated with plasma erlotinib level. These findings suggest that therapeutic drug monitoring and pharmacogenomic analysis help to prevent adverse events in cancer patients with molecular targeted therapy.

Research Products

• [Journal Article] ABCG2 421C>A polymorphism and high exposure of sunitinib in a patient with renal cell carcinoma (2010)
  • Author(s): Mizuno T, Terada T, Kamba T, Fukudo M, Katsura T, Nakamura E, Ogawa O, Inui K.
  • Journal Title: Ann Oncol 21 Pages: 1382-1383
• [Journal Article] Pharmacokinetics of erlotinib and its active metabolite OSI-420 in patients with non-small cell lung cancer and chronic renal failure who are undergoing hemodialysis (2010)
  • Author(s): Togashi Y, Masago K, Fukudo M, Terada T, Ikemi Y, Kim YH, Fujita S, Irisa K, Sakamori Y, Mio T, Inui K, Mishima M.
  • Journal Title: J Thorac Oncol 5 Pages: 601-605
• [Journal Article] Cerebrospinal fluid concentration of erlotinib and its active metabolite OSI-420 in patients with central nervous system metastases of non-small cell lung cancer (2010)
  • Author(s): Togashi Y, Masago K, Fukudo M, Terada T, Fujita S, Irisa K, Sakamori Y, Kim YH, Mio T, Inui K, Mishima M
  • Journal Title: J Thorac Oncol 5 Pages: 950-955
• [Journal Article] Good clinical response to erlotinib in a non-small cell lung cancer patient harboring multiple brain metastases and a double active somatic epidermal growth factor gene mutation (2010)
  • Author(s): Masago K, Togashi Y, Fukudo M, Terada T, Irisa K, Sakamori Y, Fujita S, Kim YH, Mio T, Inui K, Mishima M.
  • Journal Title: Case Rep Oncol 3 Pages: 98-105
• [Journal Article] Good clinical response to erlotinib in a non-small cell lung cancer patient harboring multiple brain metastases and a double active somatic epidermal growth factor gene mutation. (2010)
  • Author(s): Masago, K.
  • Journal Title: Case Rep.Oncol. Volume: 22 Pages: 98-105
  • Peer Reviewed
• [Journal Article] A case of radiation recall pneumonitis induced by erlotinib, which can be related to high plasma concentration. (2010)
  • Author(s): Togashi, Y.
  • Journal Title: J.Thorac.Oncol. Volume: 5 Pages: 924-925
  • Peer Reviewed
• [Journal Article] Cerebrospinal fluid concentration of erlotinib and its active metabolite OSI-420 in patients with central nervous system metastases of non-small cell lung cancer. (2010)
  • Author(s): Togashi, Y.
  • Journal Title: J.Thorac.Oncol. Volume: 5 Pages: 950-955
  • Peer Reviewed
• [Journal Article] ABCG2 421C>A polymorphism and high exposure of sunitinib in a patient with renal cell carcinoma (2010)
  • Author(s): Mizuno, T.
  • Journal Title: Ann.Oncol. (in press)
  • Peer Reviewed
• [Journal Article] Pharmacokinetics of erlotinib and its active metabolite OSI-420 in patients with non-small cell lung cancer and chronic renal failure who are undergoing hemodialysis (2010)
  • Author(s): Togashi, Y.
  • Journal Title: J.Thorac.Oncol. (in press)
  • Peer Reviewed
• [Presentation] ABCG2遺伝子多型のスニチニブ体内動態に及ぼす影響と遺伝子欠損マウスを用いた薬物動態解析 (2011)
  • Author(s): 水野知行、福土将秀、寺田智祐、神波大己、中村英二郎、小川修、乾賢一、桂敏也
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
• [Presentation] Pharmacogenomics of sunitinib in patients with renal cell carcinoma and pharmacokinetic analysis in Abcg2,Abcb1a/1b and triple knockout mice (2011)
  • Author(s): Mizuno T, Fukudo M, Terada T, Kamba T, Nakamura E, Ogawa O, Inui K, Katsura T.
  • Organizer: The 112th Annual Meeting of American Society for Clinical Pharmacology and Therapeutics
  • Place of Presentation: Dallas, TX, USA
• [Presentation] 非小細胞肺癌患者におけるエルロチニブの体内動態と副作用に関する母集団解析 (2010)
  • Author(s): 福土将秀
  • Organizer: 第31回日本臨床薬理学会年会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2010-12-03
• [Presentation] Clinical pharmacokinetics of erlotinib and its active metabolite OSI-420 in patients with non-small cell lung cancer. (2010)
  • Author(s): Fukudo, M.
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮ソニックシティ(埼玉市)
  • Year and Date: 2010-10-08
• [Presentation] ABCG2遺伝子多型に関連したスニチニブの曝露量増加と毒性発現が認められた一症例 (2010)
  • Author(s): 水野知行
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山市
  • Year and Date: 2010-03-28
• [Presentation] Upregulation of multidrug resistance-associated protein 4 in the early stage of vascular invasion of hepatocellular carcinoma (2010)
  • Author(s): Higuchi K, Terada T, Fukudo M, Ogasawara, K, Katsura T, Hatano E, Ikai I, Inui K.
  • Organizer: 2010 ASCO Annual Meeting
  • Place of Presentation: Chicago, IL, USA
• [Presentation] Clinical pharmacokinetics of erlotinib and its active metabolite OSI-420 in patients with non-small cell lung cancer (2010)
  • Author(s): Fukudo M, Togashi Y, Masago K, Terada T, Katsura T, Kim KH, Mio T, Mishima M, Inui K.
  • Organizer: The 25th JSSX Annual Meeting
  • Place of Presentation: Omiya
• [Presentation] ABCG2遺伝子多型のスニチニブ血中濃度に及ぼす影響 (2010)
  • Author(s): 水野知行、寺田智祐、神波大己、福土将秀、桂敏也、中村英二郎、小川修、乾賢一
  • Organizer: 第48回日本癌治療学会学術集会
  • Place of Presentation: 京都
• [Presentation] 質量分析法を用いた経口チロシンキナーゼ阻害薬6種の一斉定量法の確立 (2010)
  • Author(s): 水野知行、増田智先、石橋直哉、福土将秀、矢野育子、乾賢一、桂敏也
  • Organizer: 第20回日本医療薬学会年会
  • Place of Presentation: 千葉
• [Presentation] 非小細胞肺癌患者におけるエルロチニブの体内動態と副作用に関する母集団解析 (2010)
  • Author(s): 福土将秀、池見泰明、寺田智祐、桂敏也、乾賢一、冨樫庸介、真砂勝泰、金永学、三尾直士、三嶋理晃
  • Organizer: 第31回日本臨床薬理学会年会
  • Place of Presentation: 京都
• [Presentation] Comprehensive analysis for the expression of drug transporters in hepatocellular carcinoma (2009)
  • Author(s): Higuchi, K.
  • Organizer: 24th JSSX Annual Meeting
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2009-11-28
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