非小細胞肺癌におけるゲフィチニブの無作為化比較試験とトランスレーショナルリサーチ

2006 Fiscal Year Annual Research Report

• Project/Area Number: 16390238
• Research Institution: Kinki University
• Principal Investigator: 福岡 正博 近畿大学, 医学部附属病院, 教授 (20047202)
• Co-Investigator(Kenkyū-buntansha): 田村 研治 近畿大学, 医学部附属病院, 講師 (60340783) ; 樋田 豊明 愛知県立がんセンター, 副部長 (80250249) ; 中川 和彦 近畿大学, 医学部, 助教授 (40298964)
• Keywords: 肺がん / 非小細胞がん / 化学療法 / ゲフィチニブ / 上皮成長因子受容体 / HER2 / インスリン様成長因子I受容体 / 遺伝子変異

Research Abstract

我々は平成15年3月より進行非小細胞肺癌を対象とし、標準的治療であるプラチナを含む2剤併用化学療法群とその後にゲフィチニブを維持療法として投与する群を比較する多施設共同無作為化比較試験を行ってきた。この試験は、組織型、病期、性、化学療法の内容、PS、施設を動的割付因子として化学療法群(A群)と化学療法後のゲフィチニブ維持療法群(B群)に割り付け600例を集積することとし、平成17年5月までに604例を集積して終了した。このうち解析対象例は577例(A群287例、B群290例)であった。本年度はゲフィチニブ維持療法群から103例の腫瘍検体を回収し、腫瘍組織のヒト上皮成長因子受容体I、II(EGFR、HER2)、そのリン酸化レベル(pEGFR、pHER2)、及びインスリン類似成長因子I受容体(IGF-IR)の免疫組織染色による発現量の解析、EGFRの遺伝子変異を検索し、奏効度、無再発生存期間(TTP)との相関関係を検討した。102例の内容は、女性58%、腺癌83%、非喫煙者55%、98例が評価可能症例であった。解析の結果では、41例(42%)にEGFRの遺伝子変異が見られ14例がエクソン19の欠失、27例がエクソン21の点突然変異であった。遺伝子変異のある症例とない症例の有効率は62%と26%(p=0.002)、TTPは10.1ヶ月と5.1ヶ月(HR 0/64;P=0.048)で有意な差が認められた。pEGFRの発現およびpHER2の発現度はEGFRの遺伝子変異の頻度と相関していた。以上より、非小細胞肺癌の腫瘍組織のリン酸化EGFRの発現量の測定からEGFRの遺伝子変異の有無を知ることが可能であり、それによってEGFRチロシンキナーゼ阻害剤の有効性を予測することができると考えた。

Research Products

• [Journal Article] Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatinplus vinorelbine for advanced non-small-cell lung cancer : Four-Arm Cooperative Study in Japan. (2007)
  • Author(s): Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M.
  • Journal Title: ann. Oncol. 18(2) Pages: 317-23
• [Journal Article] Genomic profiling of malignant pleural mesothelioma with array-based comparative genomic hybridization shows frequent non-random chromosomal alteration regions including JUN amplification on 1p32. (2007)
  • Author(s): Taniguchi T, Karnana S, Fukui T, Yokoyama T, Tagawa H, Yokoi K, Ueda Y, Mitsudomi T, Horio Y, Hida T, Yatabe Y, Seto M, Sekido Y.
  • Journal Title: Cancer Sci. 98(3) Pages: 438-46
• [Journal Article] Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. (2006)
  • Author(s): Kosaka T, Yatabe Y, Endoh H, Yoshida K, Hida T, Tsuboi M, Tada H, Kuwano H, Mitsudomi T.
  • Journal Title: Clin Cancer Res. 12(19) Pages: 5764-5769
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. (2006)
  • Author(s): Ando M, Okamoto I, Yamamoto N, Takeda K, Tamura K, Seto T, Ariyoshi Y, Fukuoka M.
  • Journal Title: J Clin Oncol. 24(16) Pages: 2549-2556
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Establishment and characterization of four malignant pleural mesot helioma cell lines from Japanese patients. (2006)
  • Author(s): Usami N, Fukui T, Kondo M, Tanigutchi T, Yokoyama T, Mori S, Yokoi K, Horio Y, Shimokata K, Sekido Y, Hida T.
  • Journal Title: Cancer Sci. 97(5) Pages: 387-94
• [Journal Article] Small interfering RNA targeting survivin sensitizes lung cancer cell with mutant p53 to adriamycin. (2006)
  • Author(s): Yonesaka K, Tamura K, Kurata T, Satoh T, Ikeda M, Fukuoka M, Nakagawa K.
  • Journal Title: Int J Cancer. 118 Pages: 812-820
• [Journal Article] Phase II study of weekly paclitaxel for Relapsed and refractory small cell lung cancer. (2006)
  • Author(s): Yamamoto N, Tsurutani J, Yoshimura N, Asai G, Moriyama A, Nakagawa K, Kudou S, Takada M, Minato Y, Fukuoka M.
  • Journal Title: Anticancer Res. 26 Pages: 777-781
• [Journal Article] A EGFR mutation in gefitinib-responsive small-cell lung cancer. (2006)
  • Author(s): Okamoto I, Araki J, Suto R, Shimada M, Nakagawa K, Fukuoka M.
  • Journal Title: Ann Oncol. 17 Pages: 1028-1029
• [Journal Article] Phase II Study of Etoposide and Cisplatin With Concurrent Twice-Daily Thoracic Radiotherapy Followed by Irinotecan and Cisplatin in Patients With Limited-Disease Small-Cell Lung Cancer : (2006)
  • Author(s): Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, ando M, Tada T, Fukuoka M.
  • Journal Title: J Clin Oncol. 24(33) Pages: 5247-52
• [Journal Article] Randomized Phase II study of Carboplatin/Gemcitabine versus Vinorelbine/Gemcitabine in Patients With Advanced Non small Cell Lung Cancer. West Japan Thoracic Oncology Group(WJTOG) 0104. (2006)
  • Author(s): Yamamoto N, Nakagawa K, Uejima H, Sugiura T, Takada Y, Negoro S, Matsui K, Kashii T, Takada M, Nakanishi Y, Kato T, Fukuoka M..
  • Journal Title: Cancer 107 Pages: 599-605
• [Journal Article] Pemetrexed-induced edema of the eyelid. (2006)
  • Author(s): Kurata T, Tamura K, Okamoto I, Satoh T, Nakagawa K, Fukuoka M.
  • Journal Title: Lung Cancer 54 Pages: 241-242
• [Journal Article] A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours. (2006)
  • Author(s): Nakagawa K, Kudoh S, Matsui K, Negoro S, Yamamoto N, Latz J. E, Adachi S, Fukuoka M.
  • Journal Title: Br. J. Cancer 95 Pages: 677-682,
• [Journal Article] Is the Importance of Achieving Stable Disease Different between Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Cytotoxic Agents in the Second-Line Setting for Advanced Non-small Cell Lung Cancer? (2006)
  • Author(s): Kurata T, Matsuo K, Takada M, Kawahara M, Tsuji M, Matsubara Y, Otani N, Matsuyama S, Muraishi K, Fujita T, Ishikawa M, Koyano K, Okamoto I, Satoh T, Tamura K, Nakagawa K, Fukuoka M.
  • Journal Title: Journal of Thoracic Oncology 1 Pages: 684-691
• [Journal Article] EKB-569, a new irreversible epidermal growth factor receptor tyrosine kinase inhibitor, with clinical activity in patients with non-small cell lung cancer with acquired resistance to gefitinib. (2006)
  • Author(s): Yoshimura N, Kudoh S, Kimura T, Mitsuoka S, Matsuura K, Hirata K, Matsui K, Negoro S, Nakagawa K, Fukuoka M.
  • Journal Title: Lung Cancer 51 Pages: 363-368
• [Journal Article] Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer : results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904) (2006)
  • Author(s): Kudoh S, takeda K, Nakagawa K, Takada M, Katakami N, Matsui K, Shinkai T, Sawa T, Goto I, Semba H, Seto T, ando M, Satoh T, Yoshimura N, Negoro S, Fukuoka M
  • Journal Title: J Clin Oncol 24 Pages: 3657-3663
• [Journal Article] Phase I and Pharmacokinetic Study of Combination Chemotherapy Using Irinotecan and paclitaxel in Patients with Lung Cancer. (2006)
  • Author(s): Asai, G, Yamamoto, N, Kurata, T, Tamura, K, Uejima, H, Nakagawa, K, Fukuoka, M.
  • Journal Title: J Thorac Oncol. 1 Pages: 226-230
• [Journal Article] A Phase I Study of Irinotecan in Combination with Amrubicin for Advanced Lung Cancer Patients. (2006)
  • Author(s): Kaneda, H, Kurata, T, Tamura, K, Uejima, H, Nakagawa, K, Fukuoka, M.
  • Journal Title: Anticancer Res. 26 Pages: 2479-2486