2006 Fiscal Year Final Research Report Summary
A randomized study to evaluate survival benefit of gefitinib in patients with advanced non-small cell lung cancer and correlation of efficacy and biomarkers
Project/Area Number |
16390238
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Kinki University |
Principal Investigator |
FUKUOKA Masahiro Kinki University, Hospital, Professor, 医学部附属病院, 教授 (20047202)
|
Co-Investigator(Kenkyū-buntansha) |
TAMURA Kenji Kinki University, Hospital, Lecturer, 医学部附属病院, 講師 (60340783)
HIDA Toyoaki Prefectural Aichi Cancer Center, Assistant director, 副部長 (80250249)
NAKAGAWA Kazuhiko Kinki University, School of Medicine, Associate professor, 医学部, 助教授 (40298964)
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Project Period (FY) |
2004 – 2006
|
Keywords | Lung Cancer / non-small cell cancer / chemotherapy / gefitinib / EGFR / mutation / HER2 / IGFR-1 |
Research Abstract |
This study was a randomized trial to evaluate the survival benefit of gefitinib, a epidermal growth factor receptor (EGFR) tylosine kinase inhibitor as a maintenance therapy in advanced non-small cell lung cancer (NSCLC). Between March 2003 and July 2005, 604 patients with stage IIIB or IV NSCLC were randomly assigned to receive standard chemotherapy alone or 3 cycles of chemotherapy followed by gefitinib until disease progressin. We carried out a correlative study to determine the relationships between EGFR mutations, EGFR or HER2 protein expressions, their activation status (pEGFR, pHER2) or insulin-like growth factor receptor 1 (IGFR-1) protein expressions and clinical outcomes after gefitinib treatment. Primary endpoint was to detect biomarkers to predict gefitinib sensitivity. One hundred and three consecutive patients were enrolled onto the study. Median age was 68 years, female (58%), adenocarcinoma (83%), and never smoker (55%). 98 patients were evaluable for efficacies, toxicities and gene analyses. Forty-one pts (42%) had EGFR mutations ; 14 pts had deletional mutation in exon 19, 27 pts had missense mutation (L858R) in exon 21. EGFR mutations were significantly related to response (62 vs. 26% ; P = 0.001), disease control rate (92 vs. 65% ; P = 0.003) and TTP (median, 10.1 vs. 5.1months ; hazard ratio = 0.64 ; P = 0.048). Both pEGFR (0, +1 vs. ?+2 ; P = 0.002,) and pHER2 (0 vs. ?+1 ; P = 0.001) expressions were significantly associated with incidence of EGFR mutation. Conclusion : EGFR mutation was a significant predictive biomarker of response to gefitinib. Phosphorylated EGFR protein expression is a potent replaceable biomarker for EGFR mutation.
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Research Products
(50 results)
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[Journal Article] Randomized phase III study of cisplatin plus irinotecan versus carb oplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus 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.
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Journal Title
Ann. Oncol. 18(2)
Pages: 317-323
Description
「研究成果報告書概要(和文)」より
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[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, Karnan S, Fukui T, Yokoyama T, Tagawa H, Yokoi K, Ueda Y, Mitsudomi T, Horio Y, Hida T, Yatabe Y, Seto M, Sekido Y
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Journal Title
Cancer Sci. 98(3)
Pages: 438-446
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus 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
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Journal Title
Ann.Oncol. 18(2)
Pages: 317-23
Description
「研究成果報告書概要(欧文)」より
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[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, Karnan S, Fukui T, Yokoyama T, Tagawa H, Yokoi K, Ueda Y, Mitsudomi T, Horio Y, Hida T, Yatabe Y, Seto M, Sekido Y.
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Journal Title
Cancer Sci. 98(3)
Pages: 438-46
Description
「研究成果報告書概要(欧文)」より
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[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, Taniguchi T, Yokoyama T, Mori S, Yokoi K, Horio Y, Shimokata K, Sekido Y, Hida T
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Journal Title
Cancer Sci. 97(5)
Pages: 387-394
Description
「研究成果報告書概要(和文)」より
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[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 Cancer2006
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
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Journal Title
J Clin Oncol. 24(33)
Pages: 5247-5252
Description
「研究成果報告書概要(和文)」より
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[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.
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Journal Title
Cancer 107
Pages: 599-605
Description
「研究成果報告書概要(和文)」より
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[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.
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Journal Title
Journal of Thoracic Oncology 1
Pages: 684-691
Description
「研究成果報告書概要(和文)」より
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[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.
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Journal Title
Lung Cancer 51
Pages: 363-368
Description
「研究成果報告書概要(和文)」より
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[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
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Journal Title
J Clin Oncol 24
Pages: 3657-3663
Description
「研究成果報告書概要(和文)」より
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[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.
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Journal Title
J Thorac Oncol. 1
Pages: 226-230
Description
「研究成果報告書概要(和文)」より
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[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.
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Journal Title
Anticancer Res. 26
Pages: 2479-2486
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Establishment and characterization of four malignant pleural mesothelioma cell lines from Japanese patients.2006
Author(s)
Usami N, Fukui T, Kondo M, Taniguchi T, Yokoyama T, Mori S, Yokoi K, Horio Y, Shimokata K, Sekido Y, Hida T.
-
Journal Title
Cancer Sci. 97(5)
Pages: 387-394
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
[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 : West Japan Thoracic Oncology Group 9902.2006
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: 5247-5252
Description
「研究成果報告書概要(欧文)」より
-
-
-
[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
Description
「研究成果報告書概要(欧文)」より
-
[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
Description
「研究成果報告書概要(欧文)」より
-
[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.
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Journal Title
J Thorac Oncol. (1)
Pages: 226-230
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Irinotecan and etoposide for previously untreated extensive-disease small cell lung cancer : A phase II trial of West Japan Thoracic Oncology Group.2005
Author(s)
Kudoh S, Nakamura S, Nakano T, Komuta K, Isobe T, Katakami N, Fukuda Y, Takada Y, Takada M, Fukuoka M, Ariyoshi Y
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Journal Title
Lung Cancer. 49
Pages: 263-269
Description
「研究成果報告書概要(和文)」より
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[Journal Article] A phase I/II study comparing regimen schedules of gemcitabine and docetaxel in Japanese patients with stage IIIB/IV non-small cell lung cancer.2005
Author(s)
Mtatsui K, Hirashima T, Nitta T, Kobayashi M, Ogata Y, Furukawa M, Kudoh S, Yoshimura N, Mukohara T, Yamauchi S, Shiraishi S, Kamoi H, Negoro S, Takeda K, Nakagawa K, Takada M, Yana T, Fukuoka M
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Journal Title
Jpn J Clin Oncol. 35
Pages: 181-187
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Phase I-II study of amrubicin and cisplatin in previously untreated patients with extensive-stage small-cell lung cancer.2005
Author(s)
Ohe Y, Negoro S, Matsui K, Nakagawa K, Sugiura T, Takada Y, Nishiwaki Y, Yokota S, Kawahara M, Saijo N, Fukuoka M, Ariyoshi Y
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Journal Title
Ann Oncol. 16
Pages: 430-436
Description
「研究成果報告書概要(和文)」より
-
-
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[Journal Article] Irinotecan and etoposide for previously untreated extensive-disease small cell lung cancer : A phase II trial of West Japan Thoracic Oncology Group.2005
Author(s)
Kudoh S, Nakamura S, Nakano T, Komuta K, Isobe T, Katakami N, Fukuda Y, Takada Y, Takada M, Fukuoka M, Ariyoshi Y.
-
Journal Title
Lung Cancer 49
Pages: 263-269
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] A phase I/II study comparing regimen schedules of gemcitabine and docetaxel in Japanese patients with stage IIIB/IV non-small cell lung cancer.2005
Author(s)
Matsui K, Hirashima T, Nitta T, Kobayashi M, Ogata Y, Furukawa M, Kudoh S, Yoshimura N, Mukohara T, Yamauchi S, Shiraishi S, Kamoi H, Negoro S, Takeda K, Nakagawa K, Takada M, Yana T, Fukuoka M.
-
Journal Title
Jpn J Clin Oncol 35
Pages: 181-187
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Phase I-II study of amrubicin and cisplatin in previously untreated patients with extensive-stage small-cell lung cancer.2005
Author(s)
Ohe Y, Negoro S, Matsui K, Nakagawa K, Sugiura T, Takada Y, Nishiwaki Y, Yokota S, Kawahara M, Saijo N, Fukuoka M, Ariyoshi Y.
-
Journal Title
Ann Oncol. 16
Pages: 430-436
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Randomized phase II study of docetaxel/ cisplatin versus docetaxel / irinotecan in advanced non-small cell lung cancer : a West Japan Thoracic Oncology Study (WJTOG9803).2004
Author(s)
Yamamoto, N., Fukuoka, M., Negoro, S., Nakagawa, K., Saito, H., Matsui, K., Kawahara, M., Senba, H., Takada, Y., Kudoh, S., Nakano, T., Katakami, N., Sugiura, T., Hoso, T., Ariyoshi, Y.
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Journal Title
Br J Cancer. 90
Pages: 87-92
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Effect of re-treatment with gefitinib ('Iressa', ZD1839) after accuisition of resistance.2004
Author(s)
Kurata, T., Tamura, K., Kaneda, H., Nogami, T., Uejima, H., Asai, G., Nakagawa, K., Fukuoka, M.
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Journal Title
Ann Oncol. 15
Pages: 173-174
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Combination phase I study of nedaplatin and gemcitabine for advanced non-small-cell lung cancer.2004
Author(s)
Kurata, T., Tamura, K., Yamamoto, N., Nogami, T., Satoh, T., Kaneda, H., Nakagawa, K., Fukuoka, M.
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Journal Title
Br J Cancer. 90
Pages: 2092-2096
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Retrospective analysis of the predictive factors associated with the response and survival benefit of gefitinib in patients with advanced non-small-cell lung cancer.2004
Author(s)
Kaneda, H., Tamura, K., Kurata, T., Uejima, H., Nakagawa, K., Fukuoka, M.
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Journal Title
Lung Cancer. 46
Pages: 247-254
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839).2004
Author(s)
Kakiuchi, S., Daigo, Y., Ishikawa, N., Furukawa, C., Tsunoda, T., Yano, S., Nakagawa, K., Tsuruo, T., Kohno, N., Fukuoka, M., Sone, S., Nakamura, Y.
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Journal Title
Hum Mol Genet. 13
Pages: 3029-3043
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Interferon-gamma differentially regulates susceptibility of lung cancer cells to telomerase-specific cytotoxic T lymphocytes.2004
Author(s)
Tajima K, Ito Y, Demachi A, Nishida K, Akatsuka Y, Tsujimura K, Hida T, Morishima Y, Kuwano H, Mitsudomi T, Takahashi T, Kuzushima K
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Journal Title
Int J Cancer. 110(3)
Pages: 403-412
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Randomized phase II study of docetaxel/ cisplatin versus docetaxel/ irinotecan in advanced non-small cell lung cancer : a West Japan Thoracic Oncology Study (WJT0G9803).2004
Author(s)
Yamamoto, N., Fukuoka, M., Negoro, S., Nakagawa, K., Saito, H., Matsui, K., Kawahara, M., Senba, H., Ta kada, Y., Kudoh, S., Nakano, T., Katakami, N., Sugiura, T., Hoso, T., Ariyoshi, Y.for the West Japan Thora cic Oncology Group.
-
Journal Title
Br J Cancer. 90
Pages: 87-92
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Effect of re-treatment with gefitinib (' Iressa', ZD1839) after acquisition of resistance.2004
Author(s)
Kurata, T., Tamura, K., Kaneda, H., Nogami, T., Uejima, H., Asai, G., Nakagawa, K., Fukuoka, M.
-
Journal Title
Ann Oncol. 15
Pages: 173-174
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Combination phase I study of nedaplatin and gemcitabine for advanced non-small-cell lung cancer2004
Author(s)
Kurata, T., Tamura, K., Yamamoto, N., Nogami, T., Satoh, T., Kaneda, H., Nakagawa, K., Fukuoka, M.
-
Journal Title
Br J Cancer. 90
Pages: 2092-2096
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Interferon-gamma differentially regulates susceptibility of lung cancer cells to telomerase- specific cytotoxic T lymphocytes. Int J Cancer.2004
Author(s)
Tajima K, Ito Y, Demachi A, Nishida K, Akatsuka Y, Tsujimura K, Hida T, Morishima Y, Kuwano H, Mitsudomi T, Takahashi T, Kuzushima K.
-
Journal Title
Description
「研究成果報告書概要(欧文)」より