The usefulness of chemotherapy with S-1 for Japanese patients with non-small-cell lung cancer based on CYP2A6*4 gene polymorphism

• Project/Area Number: 20590536
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: INUI Naoki Hamamatsu University School of Medicine, 医学部・臨床薬理学, 助教 (80402254)
• Co-Investigator(Kenkyū-buntansha): WATANABE Hiroshi 浜松医科大学, 医学部, 教授 (50262803) ; CHIDA Kingo 浜松医科大学, 医学部, 准教授 (40197611)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 薬物治療学 / 薬物代謝酵素 / 個別化治療 / 抗癌剤S-1 / 肺癌 / CYP2A6 / 抗癌剤S1

Research Abstract

The frequencies of the CYP2A6^*4C was 17.4%. In the S-1 pharmacokinetic analysis, the area under the concentration-time curve from 0 to 10 hours (AUC) ratios of 5-FU/tegafur showed large interindividual variabilities, ranging from 5.14 to 112.6. The AUC for tegafur was 1.5-fold higher in patients with the CYP2A6^*4C allele than in patients without the CYP2A6^*4C allele. Patients with the CYP2A6^*4C allele had a significantly lower maximum plasma concentration for 5-FU than patients without the CYP2A6^*4C allele.

Research Products

• [Journal Article] Phase II study of combination chemotherapy with S-1 and weekly cisplatin in patients with previously untreated advanced non-small cell lung cancer. (2009)
  • Author(s): Ozawa Y, Inui N, Naitoh T, Yasuda K, Nagayama M, Shirai T, Suganuma H, Fujii M, Nakamura H, Suda T, Chida K.
  • Journal Title: Lung Cancer. 63 Pages: 68-71
  • Peer Reviewed
• [Journal Article] Effect of thyroid hormone on the activity of CYP3A enzyme in humans. (2009)
  • Author(s): Takahashi N, Inui N, Morita H, Takeuchi K, Uchida S, Watanabe H, Nakamura H.
  • Journal Title: J Clin Pharmacol. 50 Pages: 88-93
  • Peer Reviewed
• [Journal Article] Effects of statins on the pharmacokinetics of midazolam in healthy volunteers. (2009)
  • Author(s): Kokudai M, Inui N, Takeuchi K, Sakaeda T, Kagawa Y, Watanabe H.
  • Journal Title: J Clin Pharmacol. 49 Pages: 568-573
  • Peer Reviewed
• [Journal Article] The CYP2A6*4 allele is determinant of S-1 pharmacokinetics in Japanese patients with non-small-cell lung cancer (2008)
  • Author(s): Kaida Y, Inui N, Suda T, Nakamura H, Watanabe H, Chida K
  • Journal Title: Clin Pharmacol Ther 83 Pages: 589-594
  • Peer Reviewed
• [Journal Article] 非小細胞肺癌患者における薬物代謝酵素CYP2A6遺伝子多型の存在とS-1の薬物動態に及ぼす影響 (2008)
  • Author(s): 貝田勇介, 乾直輝, 渡邉裕司
  • Journal Title: 臨床薬理の進歩 29 Pages: 81-87
  • Peer Reviewed
• [Journal Article] Response to "The Unanswered Question : What Is the Determinant of S-1 Pharmacokinetics? (2008)
  • Author(s): Kaida Y, Inui N, Suda T, Watanabe H, Chida K.
  • Journal Title: Clin Pharmacol Ther 84 Pages: 204-204
  • Peer Reviewed
• [Journal Article] 非小細胞肺癌患者における薬物代謝酵素CYP2A6遺伝子多型の存在とS-1の薬物動態に及ぼす影響 (2008)
  • Author(s): 貝田勇介
  • Journal Title: 臨床薬理の進歩 29 Pages: 81-87
  • Peer Reviewed
• [Journal Article] The CYP2A6^*4 allele is determinant of S-1 pharmacokinetics in Japanese patients with non-small-cell lung cancer. (2008)
  • Author(s): Kaida Y.
  • Journal Title: Clin Pharmacol Ther 83 Pages: 589-594
  • Peer Reviewed
• [Presentation] 非小細胞肺癌患者におけるCYP2A6遺伝子多型とS-1の薬物動態 (2008)
  • Author(s): 乾直輝
  • Organizer: 日本臨床薬理学会年会
  • Place of Presentation: 東京
• [Presentation] The Influence of CYP2A6 Gene Polymorphism on S-1 Therapy in Non-Small-Cell Lung Cancer Patients. (2008)
  • Author(s): Kaida Y, Inui N.
  • Organizer: American Thoracic Society.
  • Place of Presentation: Toronto