Individualized treatment of lung cancer based on the resistant mutation in EGFR gene from circulating tumor cells

• Project/Area Number: 22790746
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Tohoku University
• Principal Investigator: INOUE Akira 東北大学, 病院, 特任准教授 (70361087)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: EGFR / 個別化治療 / 循環腫瘍細胞 / EGFRチロシンキナーゼ阻害剤 / EGFR遺伝子変異 / PNA-LNA PCRクランプ法

Research Abstract

Prospective study of individualized treatment for lung cancer resistant to epidermal growth factor receptor tyrosine kinase based on the T790M resistant mutation status detected from DNA of circulating tumor cells (CTC) was conducted. At the point when 6 enrolled patients were analyzed, it was revealed that the positive rate of CTC was quite lower than expected and that obtained DNA of CTC was too small to detect the T790M mutation. Thus the study was terminated halfway.

Research Products

• [Journal Article] LUX-Lung 4: A Phase II Trial of Afatinib in Patients withAdvanced, Non-Small Cell Lung Cancer who progressed on Prior Treatment with Erlotinib, Gefitinib, or Both (2013)
  • Author(s): Katakami N, Atagi S, Inoue A, et al
  • Journal Title: J Clin Oncol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Impact of epidermal growth factor receptor inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis (2013)
  • Author(s): Lee CK, Brown C, Inoue A, et al
  • Journal Title: J Natl Cancer I Volume: 105 Issue: 9 Pages: 595-605
  • DOI: 10.1093/jnci/djt072
  • Peer Reviewed
• [Journal Article] Interstitial Lung Disease associated with Gefitinib in Japanese Patients with EGFR MutatedNon-Small Cell Lung Cancer: Combined analysis of two phase III trials (NEJ 002 and WJTOG 3405) (2013)
  • Author(s): Akamatsu H, Inoue A, Mitsudomi T, et al
  • Journal Title: Jpn Clin Oncol Volume: 43 Issue: 6 Pages: 664-8
  • DOI: 10.1093/jjco/hyt049
  • Peer Reviewed
• [Journal Article] Updated Overall Survival Results from A Randomized Phase III Trial Comparing Gefitinib with Carboplatin-Paclitaxel for Chemo-Naive Non-Small Cell Lung Cancer with Sensitive EGFR Gene Mutations (NEJ002) (2013)
  • Author(s): Inoue A, Kobayashi K, Maemondo M, et al
  • Journal Title: Ann Oncol Volume: 24 Issue: 1 Pages: 54-9
  • DOI: 10.1093/annonc/mds214
  • Peer Reviewed
• [Journal Article] LUX-Lung 4: A Phase II Trial of Afatinib in Patients with Advanced, Non-Small Cell Lung Cancer who Progressed on Prior Treatment with Erlotinib, Gefitinib, or Both. (2013)
  • Author(s): Katakami N
  • Journal Title: J Clin Oncol Volume: in press
  • Peer Reviewed
• [Journal Article] Quality of Life with Gefitinib in Patients with EGFR-Mutated Non-Small Cell Lung Cancer : Quality of Life Analysis of North East Japan Study Group 002 Trial (2012)
  • Author(s): Oizumi S, Kobayashi K, Inoue A, Maemondo M, Sugawara S, Yoshizawa H, Isobe H, Harada M, Kinoshita I, Okinaga S, Kato T, Harada T, Gemma A, Saijo Y, Yokomizo Y, Morita S, Hagiwara K, Nukiwa T.
  • Journal Title: Oncologist Volume: 17 Issue: 6 Pages: 863-70
  • DOI: 10.1634/theoncologist.2011-0426
  • Peer Reviewed
• [Journal Article] First-Line Gefitinib in Patients Aged 75 or Older With Advanced Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations: NEJ 003 Study (2012)
  • Author(s): Maemondo M, Minegishi Y, Inoue A, et al
  • Journal Title: J Thorac Oncol Volume: 7 Pages: 1417-22
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22895139
  • Peer Reviewed
• [Journal Article] (2012)
  • Author(s): Soda M, Isobe K, Inoue A, Maemondo M,Oizumi S, Fujita Y, Gemma A, Yamashita Y,Ueno T, Takeuchi K, Choi YL, Miyazawa H,Tanaka T, Hagiwara K, Mano H
  • Journal Title: Clin Cancer Res Volume: 18 Issue: 20 Pages: 5682-5689
  • DOI: 10.1158/1078-0432.ccr-11-2947
  • Peer Reviewed
• [Journal Article] Miliary brainmetastases in 2cases with advanced non-small cell lung cancer harboring EGFR mutation during gefitinib treatment (2012)
  • Author(s): Mochizuki S, Nishimura N, Inoue A, et al
  • Journal Title: Respiratory Investigation Volume: 50 Issue: 3 Pages: 117-21
  • DOI: 10.1016/j.resinv.2012.06.002
  • Peer Reviewed
• [Journal Article] Runx1-deficiency in CD4+ T Cells Causes Fatal Autoimmune Inflammatory Lung Disease due to Spontaneous Hyperactivation of Cells (2012)
  • Author(s): Wong WF
  • Journal Title: J. Immunol. Volume: 188 Issue: 10 Pages: 5408-5420
  • DOI: 10.1038/bjc.2012.422
  • Peer Reviewed
• [Journal Article] First-Line Gefitinib in Patients Aged 75 or Older With Advanced Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations: NEJ 003 Study. (2012)
  • Author(s): Maemondo M
  • Journal Title: J Thorac Oncol Volume: 7 Pages: 1417-1422
  • Peer Reviewed
• [Journal Article] 肺がんの分子標的治療薬 (2012)
  • Author(s): 井上彰
  • Journal Title: 日本老年医学会雑誌 Volume: 49 Pages: 8-13
  • NAID: 10030470073
• [Journal Article] Low-dose gefitinib treatment for patients with advanced non-small cell lung cancer harboring sensitive epidermal growth factor receptor mutations (2011)
  • Author(s): Satoh H, Inoue A, Kobayashi K, Maemondo M, Oizumi S, Isobe H, Gemma A, Saijo Y, Yoshizawa H, Hagiwara K, Nukiwa T
  • Journal Title: J Thorac Oncol Volume: 6(8) Issue: 8 Pages: 1413-7
  • DOI: 10.1097/jto.0b013e31821d43a8
  • Peer Reviewed
• [Journal Article] Optimization of Dosing for EGFR-Mutant Non-Small Cell LungCancer with Evolutionary CancerModeling (2011)
  • Author(s): Chmielecki J, Foo J, Inoue A, et al
  • Journal Title: Sci Transl Med Volume: 3 Issue: 90
  • DOI: 10.1126/scitranslmed.3002356
  • Peer Reviewed
• [Journal Article] Phase II study of Gefitinib Readministration in Patients with Advanced Non-Small Cell Lung Cancer and Previous Response to Gefitinib (2011)
  • Author(s): Asahina H, Oizumi S, Inoue A, et al
  • Journal Title: Oncology-BASEL Volume: 79 Issue: 5-6 Pages: 423-429
  • DOI: 10.1159/000326488
  • NAID: 120003025344
  • Peer Reviewed
• [Journal Article] Low-dose Gefitinib Treatment for Patients with Advanced Non-small Cell Lung Cancer Harboring Sensitive Epidermal Growth Factor Receptor Mutations (2011)
  • Author(s): Satoh H, Inoue A, et al
  • Journal Title: J Thorac Oncol Volume: 6 Pages: 1413-1417
  • Peer Reviewed
• [Journal Article] Randomized Phase II Study of Two Schedules of Carboplatin and Gemcitabine for Stage IIIB and IV Advanced Non-Small Cell Lung Cancer (JACCRO LC-01 Study) (2011)
  • Author(s): Imamura F, Inoue A, 6番目, et al
  • Journal Title: Chemotherapy Volume: 57 Issue: 4 Pages: 357-362
  • DOI: 10.1159/000330481
  • Peer Reviewed
• [Journal Article] A phase II study of amrubicin combined with carboplatin for elderly patients with small-cell lung cancer.North Japan Lung Cancer Study Group Trial 0405. (2010)
  • Author(s): Inoue A, et al
  • Journal Title: Ann Oncol Volume: 21 Pages: 800-803
  • Peer Reviewed
• [Journal Article] Randomized, phase II trial of weekly paclitaxel combined with carboplatin versus standard paclitaxel combined with carboplatin for elderly patients with advanced non-small-cell lung cancer. (2010)
  • Author(s): Sakakibara T, Inoue A, et al
  • Journal Title: Ann Oncol Volume: 21 Pages: 795-799
  • Peer Reviewed
• [Journal Article] Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. (2010)
  • Author(s): Maemondo M, Inoue A, et al
  • Journal Title: N Engl J Med Volume: 362 Pages: 2380-2388
  • Peer Reviewed
• [Presentation] クリゾチニブによる薬剤性肺障害を発症した後、同剤を再投与した一例 (2013)
  • Author(s): 井上彰、ほか
  • Organizer: 第96回日本呼吸器学会東北地方会
  • Place of Presentation: 秋田
  • Year and Date: 2013-03-23
• [Presentation] 肺癌治療に関連する臨床的な知見 (2013)
  • Author(s): 井上彰
  • Organizer: 第32回日本画像医学会教育講演15
  • Place of Presentation: 東京
  • Year and Date: 2013-02-23
• [Presentation] 進行肺がんの薬物療法 (2012)
  • Author(s): 井上彰
  • Organizer: 第7回医療の質・安全学会学術集会シンポジウム10
  • Place of Presentation: 大宮
  • Year and Date: 2012-11-24
• [Presentation] EGFR-TKIが教えてくれたこと (2012)
  • Author(s): 井上彰
  • Organizer: 第53回日本肺癌学会総会シンポジウム1
  • Place of Presentation: 岡山
  • Year and Date: 2012-11-08
• [Presentation] Randomized phase II trial comparing carboplatin with weekly paclitaxel and docetaxel alone for elderly patients with non-small cell lung cancer:NJLCG0803 (2012)
  • Author(s): 井上彰 、ほか
  • Organizer: 第10回日本臨床腫瘍学会International session7
  • Place of Presentation: 大阪
  • Year and Date: 2012-07-28
• [Presentation] クリゾチニブによる急性肺障害の一例 (2012)
  • Author(s): 井上彰、ほか
  • Organizer: 第51回日本肺癌学会東北支部会
  • Place of Presentation: 弘前
  • Year and Date: 2012-07-21
• [Presentation] 臨床論文の書き方 (2012)
  • Author(s): 井上彰
  • Organizer: 第7回日本緩和医療薬学会教育セミナー
  • Place of Presentation: 東京
  • Year and Date: 2012-06-29
• [Presentation] EGFR (2012)
  • Author(s): 井上彰
  • Organizer: 第38回肺癌診断会シンポジウム2
  • Place of Presentation: 越後湯沢
  • Year and Date: 2012-06-23
• [Presentation] 分子標的治療 (2012)
  • Author(s): 井上彰
  • Organizer: 第29回日本呼吸器外科学会総会教育講演
  • Place of Presentation: 秋田
  • Year and Date: 2012-05-17
• [Presentation] Molecular mechanisms of resistance to EGFR-TKI (2011)
  • Author(s): Inoue A
  • Organizer: 16^<th> Congress of APSR (Symposium 18)
  • Place of Presentation: Shanghai, China
  • Year and Date: 2011-11-06
• [Presentation] Evidences ofEGFR-targeted therapy for NSCLC in Asia (2011)
  • Author(s): Inoue A
  • Organizer: 16^<th> Congress of APSR (Symposium 16)
  • Place of Presentation: Shanghai, China
  • Year and Date: 2011-11-06
• [Presentation] Molecular mechanisms of resistance to EGFR-TKI (2011)
  • Author(s): Inoue A.
  • Organizer: 16^<th> Congress of APSR
  • Place of Presentation: Shanghai、中国
  • Year and Date: 2011-11-06
• [Presentation] Evidences of EGFR-targeted therapy for NSCLC in Asia (2011)
  • Author(s): Inoue A.
  • Organizer: 16^<th> Congress of APSR
  • Place of Presentation: Shanghai、中国
  • Year and Date: 2011-11-05
• [Presentation] 肺癌の分子標的治療の進歩(EGFR-TKI) (2011)
  • Author(s): 井上彰
  • Organizer: 第52回日本肺癌学会シンポジウム1
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-03
• [Presentation] 肺癌の分子標的治療の進歩(EGFR-TKI) (2011)
  • Author(s): 井上彰
  • Organizer: 第52回日本肺癌学会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-03
• [Presentation] Mutation-based clinical trials of EGFR-TKI in Japan (2011)
  • Author(s): 井上彰
  • Organizer: 第9回日本臨床腫瘍学会 International session3
  • Place of Presentation: 横浜
  • Year and Date: 2011-07-23
• [Presentation] 肺癌の臨床における抗EGFR療法の展開 (2011)
  • Author(s): 井上彰
  • Organizer: 第9回日本臨床腫瘍学会シンポジウム03
  • Place of Presentation: 横浜
  • Year and Date: 2011-07-22
• [Presentation] Mutation-based clinical trials of EGFR-TKI in Japan (2011)
  • Author(s): 井上彰
  • Organizer: 第9回日本臨床腫瘍学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-07-22
• [Presentation] 肺癌の臨床における抗EGFR療法の展開 (2011)
  • Author(s): 井上彰
  • Organizer: 第9回日本臨床腫瘍学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-07-21
• [Presentation] Final overall survival results of NEJ002, a phase III trial comparing gefitinib to carboplatin (CBDCA)plus paclitaxel (TXL) as the first-line treatment for advanced non-smallcell lung cancer (NSCLC) with EGFR mutations (2011)
  • Author(s): Inoue A, Kobayashi K, Maemondo M, et al
  • Organizer: ASCO annual meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 2011-06-06
• [Presentation] Final overall survival results of NEJ002, a phase III trial comparing gefitinib to carboplatin (CBDCA) plus paclitaxel (TXL) as the first-line treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutations (2011)
  • Author(s): Inoue A, Kobayashi K, Maemondo M, et al
  • Organizer: ASCO annual meeting 2011
  • Place of Presentation: Chicago、アメリカ
  • Year and Date: 2011-06-04
• [Presentation] 非小細胞肺癌における最近の分子標的治療薬の動向 (2011)
  • Author(s): 井上彰
  • Organizer: 第93回日本肺癌学会関西支部会
  • Place of Presentation: 神戸
  • Year and Date: 2011-02-19
• [Presentation] What we can do afterpresent TKI failure- Acquired resistance? (2010)
  • Author(s): Inoue A
  • Organizer: TSPCCM annual meeting
  • Place of Presentation: Taipei, Taipei
  • Year and Date: 2010-12-11
• [Presentation] What we can do after present TKI failure-Acquired resistance? (2010)
  • Author(s): Inoue A
  • Organizer: TSPCCM annual meeting
  • Place of Presentation: 台北,台湾
  • Year and Date: 2010-12-11
• [Presentation] Recent topics about theindividualized treatment for advanced non-small cell lung cancer (2010)
  • Author(s): Inoue A
  • Organizer: KASLC annual meeting
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-11-19
• [Presentation] Recent topics about the individualized treatment for advanced non-small cell lung cancer. (2010)
  • Author(s): Inoue A
  • Organizer: KASLC annual meeting
  • Place of Presentation: ソウル,韓国
  • Year and Date: 2010-11-18
• [Presentation] 小細胞肺がん (2010)
  • Author(s): 井上彰
  • Organizer: 第51回日本肺癌学会総会
  • Place of Presentation: 広島
  • Year and Date: 2010-11-04
• [Presentation] A final results of a phase II study of first-line gefitinib for elderly patients with advanced non-small cell lung cancer harboring epidermal growth factor receptor mutations ; NEJ 003 study. (2010)
  • Author(s): Inoue A
  • Organizer: ESMO congress
  • Place of Presentation: ミラノ,イタリア
  • Year and Date: 2010-09-25
• [Presentation] How to select patient for chemo or targeted agents. (2010)
  • Author(s): Inoue A
  • Organizer: Chinese Conference on Medical Oncology
  • Place of Presentation: 北京,中国
  • Year and Date: 2010-07-26
• [Presentation] 非小細胞肺癌に対する個別化治療の考え方 (2010)
  • Author(s): 井上彰
  • Organizer: 第49回日本肺癌学会中国・四国支部会
  • Place of Presentation: 徳島
  • Year and Date: 2010-07-17
• [Presentation] Preliminary results from a prospective study of systemic chemotherapy with carboplatin plus amrubicine for thymic malignancies.
  • Author(s): Inoue A
  • Organizer: 3rd ITMIG meeting
  • Place of Presentation: Fukuoka
• [Presentation] Randomized phase II trial comparing carboplatin with weekly paclitaxel and docetaxel alone for elderly patients with non-small cell lung cancer: NJLCG0803.
  • Author(s): 井上 彰
  • Organizer: 第10回日本臨床腫瘍学会
  • Place of Presentation: 大阪
• [Presentation] EGFR-TKIが教えてくれたこと．
  • Author(s): 井上 彰
  • Organizer: 第53回日本肺癌学会
  • Place of Presentation: 岡山
  • Invited
• [Presentation] 進行肺がんの薬物療法．
  • Author(s): 井上 彰
  • Organizer: 第7回医療の質・安全学会
  • Place of Presentation: 大宮
  • Invited
• [Presentation] 肺癌治療に関連する臨床的な知見．
  • Author(s): 井上 彰
  • Organizer: 第32回日本画像医学会
  • Place of Presentation: 東京
  • Invited