EGFR遺伝子活性型変異陽性の非小細胞肺癌患者においてゲフィチニブ治療中に認められた耐性形式の検討  [in Japanese] Retrospective Analysis of Acquired Resistance During the Treatment with Gefitinib in Non-Small Cell Lung Cancer Patients with Epidermal Growth Factor Receptor Mutations  [in Japanese]

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Author(s)

    • 佐藤 輝幸 Sato Teruyuki
    • 東北大学大学院医学系研究科呼吸器病態学分野|東北大学病院呼吸器内科 Department of Respiratory Medicine, Graduate School of Medicine, Tohoku University|Department of Respiratory Medicine, Tohoku University Hospital
    • 井上 彰 Inoue Akira
    • 東北大学病院呼吸器内科 Department of Respiratory Medicine, Tohoku University Hospital
    • 太田 洋充 Ohta Hiromitsu
    • 東北大学大学院医学系研究科呼吸器病態学分野|東北大学病院呼吸器内科 Department of Respiratory Medicine, Graduate School of Medicine, Tohoku University|Department of Respiratory Medicine, Tohoku University Hospital
    • 海老名 雅仁 Ebina Masahito
    • 東北大学大学院医学系研究科呼吸器病態学分野|東北大学病院呼吸器内科 Department of Respiratory Medicine, Graduate School of Medicine, Tohoku University|Department of Respiratory Medicine, Tohoku University Hospital
    • 貫和 敏博 Nukiwa Toshihiro
    • 東北大学大学院医学系研究科呼吸器病態学分野|東北大学病院呼吸器内科 Department of Respiratory Medicine, Graduate School of Medicine, Tohoku University|Department of Respiratory Medicine, Tohoku University Hospital

Abstract

<b>背景</b>.上皮増殖因子受容体(EGFR)チロシンキナーゼ阻害剤であるゲフィチニブは,活性型EGFR遺伝子変異を有する非小細胞肺癌患者に対して著明な抗腫瘍効果をもたらすが,後に生じる耐性化への対策は十分に検討されていない.<b>方法</b>.2004年6月∼2007年6月の間に,当施設で活性型EGFR遺伝子変異陽性と診断され,ゲフィチニブ治療が開始された進行非小細胞肺癌患者を対象に,増悪形式に関連した臨床的特徴をレトロスペクティブに解析した.<b>結果</b>.51例にゲフィチニブ治療が行われ,奏効率,病勢制御率は各々71%(36/51),86%(44/51)であった.病勢制御できた44例のうち,2008年4月末時点で33例に増悪を認め(無増悪生存期間中央値14ヶ月),21例は胸郭内,12例は遠隔臓器での増悪(うち10例は脳転移)であった.脳転移増悪例の過半数では放射線治療とともにゲフィチニブが3ヶ月以上継続され,生存期間中央値は28.2ヶ月と極めて良好であった.耐性遺伝子変異T790Mは全て原発巣近傍から検出された.<b>結論</b>.ゲフィチニブ治療例においては異なる増悪形式が認められ,それぞれの機序をふまえた治療法の開発が望まれる.<br>

<i><b>Background</b></i>. Gefitinib, a selective inhibitor of tyrosine kinase of the epidermal growth factor receptor (EGFR), can be effective in patients with non-small-cell lung cancer (NSCLC) harboring somatic mutations of EGFR. However, the clinical resistance to gefitinib is an unsolved problem. <i><b>Methods</b></i>. We analyzed patients with advanced NSCLC with EGFR mutations treated with gefitinib between June 2004 and June 2007 in our institution. The effectiveness of gefitinib, the pattern of relapse, progression-free survival (PFS), and overall survival were assessed retrospectively. EGFR mutations were all examined by DNA direct sequence or peptide nucleic acid-locked nucleic acid (PNA-LNA) polymerase chain reaction (PCR) clamp method by using the tumor specimen before treatment, and re-examination of EGFR mutations by using relapsed tumor sample was performed for some patients. <i><b>Results</b></i>. From June 2004 to June 2007, 51 patients with advanced NSCLC harboring EGFR mutations started treatment with gefitinib, and 36 had partial response and 8 had stable disease. The overall response rate and disease control rate were 71% and 86%, respectively. Among 44 responders to gefitinib, disease progression was observed in 33 patients by April 2008. The initial sites of relapse were thoracic (primary lung tumor, pleural effusion, etc) in 21 patients, and distant (brain, bone, etc) in 12 patients. There was no statistical difference in PFS among the initial sites of recurrence. T790M, a resistant mutation of EGFR, was detected in 3 specimens obtained after relapse. Interestingly, most of patients with initial relapse in the thorax had to change the treatment from gefitinib within 3 months, however, more than half of the patients with brain relapse could be managed by radiation therapy with gefitinib for over 3 months. The median survival time of patients with initial relapse in the brain was 28.2 months, which is quite better than that of general NSCLC patients with brain metastasis. <i><b>Conclusion</b></i>. Different patterns of relapse were observed in NSCLC patients treated with gefitinib. The new therapeutic strategy according to the mechanism of resistance to EGFR-TKI is warranted.<br>

Journal

  • Haigan

    Haigan 49(3), 257-261, 2009

    The Japan Lung Cancer Society

Codes

  • NII Article ID (NAID)
    130000123206
  • Text Lang
    JPN
  • ISSN
    0386-9628
  • Data Source
    J-STAGE 
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