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Study for the efficacy of'Metronomic chemotherapy' agains the gynecological cancers

Research Project

Project/Area Number 21592135
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKyushu University

Principal Investigator

KOBAYASHI Hiroaki  九州大学, 医学研究院, 准教授 (70260700)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords婦人科腫瘍学 / 婦人科がん / メトロノミック化学療法 / 婦人科癌 / がん休眠療法
Research Abstract

Recently proposed' Metronomic chemotherapy' is the new therapy using repeated administration of low dose anticancer drugs to induce' tumor dormancy state' without serious side effects against even drug-resistant tumors, based on the background that vascular endothelial cells are reproducibly susceptible to even small amount of drugs. In this study, we conducted animal experiments and clinical trials to evaluate the efficacy of metronomic chemotherapy on the gynecologic cancers. Mice bearing a paclitaxel-resistant tumor of human ovarian cancer were treated by divided-low dose or single-high dose administration of paclitaxel, and the tumor growth was more inhibited in the mice treated by the former. The toxicity was obviously mild in the mice administered by the divided-low dose. Therefore, metronomic chemotherapy seemed to be able to inhibit the tumor growth in spite of a mild side effect against drug-resistant tumors. As this reason, the divided-low dose administration of paclitaxel was found to inhibit neovascularization better than the single-high dose administration, by the experiment to evaluate the neovascularity into Matrigel. Similar results were obtained by the other anticancer drugs of docetaxel and irinotecan. Based on the theory of metronomic chemotherapy, we conducted a clinical trial of the tumor dormancy therapy by the divided-low dose anticancer drugs administered with an individualized maximum repeatable dose(iMRD). After IRB approval until now, 42 ovarian and 29 cervical cancer patients of intractable recurred cases were introduced to this study, and good QOL and relatively long TTP(time to progression) were obtained. Although the number of case is small and the follow-up period is short, the efficacy of tumor dormancy therapy applied by metronomic chemotherapy was suggested.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (35 results)

All 2011 2010 2009

All Journal Article (15 results) (of which Peer Reviewed: 13 results) Presentation (19 results) Book (1 results)

  • [Journal Article] Nuclear localizationof E-cadherin but not beta-catenin in human ovarian granulosa cell tumors and normal ovarian follicles and ovarian stroma2011

    • Author(s)
      Ohishi Y, Oda Y, Kurihara S, Kaku T, Kobayashi H, Wake N, Tsuneyoshi M
    • Journal Title

      Histopathology

      Volume: 58(3) Pages: 423-432

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Questionnaire survey of the current status of radical trachelectomy in Japan2011

    • Author(s)
      Sato S, Aoki D, Kobayashi H, et al
    • Journal Title

      Int J Clin Oncol

      Volume: 16(2) Pages: 141-144

    • NAID

      10029366477

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nuclear localization of E-cadherin but not beta-catenin in human ovarian granulosa cell tumours and normal ovarian follicles and ovarian stroma2011

    • Author(s)
      Ohishi Y, Oda Y, Kurihara S, Kaku T, Kobayashi H, et al
    • Journal Title

      Histopathology

      Volume: 58(3) Pages: 423-432

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] E-cadherin nuclear staining is useful for the diagnosis of ovarian adult granulosa cell tumor2011

    • Author(s)
      Ohishi Y, Kurihara S, Takeuchi T, Aman M, Kaku T, Kobayashi H, et al
    • Journal Title

      Hum Pathol

      Volume: (Epub ahead of print)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 妊娠合併頸癌の治療と管理2011

    • Author(s)
      小林裕明
    • Journal Title

      日本産科婦人科学会雑誌

      Volume: 63(4) Pages: 1217-1223

    • NAID

      110008593700

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 当科における腹式子宮頸部摘出術の適格基準と疾病予後について2011

    • Author(s)
      小林裕明
    • Journal Title

      日本婦人科腫瘍学会雑誌

      Volume: 29(3) Pages: 668-674

    • NAID

      10029412702

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Cytoplasmic and stromal expression of laminin? 2 chain correlates with infiltrative invasion in ovarian mucinous neoplasms of gastro-intestinaltype2010

    • Author(s)
      Okuma E, Ohishi Y, Oda Y, Aishima S, Kurihara S, Nishimura I, Yasunaga M, Kobayashi H, Wake N, Tsuneyoshi M
    • Journal Title

      Oncol Rep

      Volume: 24(6) Pages: 1569-1576

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Low-dose mithramycin exerts its anticancer effect via the p53 Signaling pathway and synergizes with nutlin-3 ingynecologic cancers2010

    • Author(s)
      Ohgami T, Kato K, Kobayashi H, Sonoda K, Inoue T, Yamaguchi S, Yoneda T, Wake N
    • Journal Title

      Cancer Sci

      Volume: 101(6) Pages: 1387-1395

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sentinel node detection with (99m)Tc phytate alone is satisfactory for cervical cancer patients undergoing radical hysterectomy and pelviclymph adenectomy2010

    • Author(s)
      Ogawa, S., Kobayashi, H., et al
    • Journal Title

      Int J Clin Oncol

      Volume: 15 Pages: 52-58

    • NAID

      10027201656

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers2010

    • Author(s)
      Ohgami, T., Kato, K., Kobayashi, H., et al
    • Journal Title

      Cancer Sci

      Volume: 101 Pages: 1387-1395

    • NAID

      10026593277

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Incidence of postmolar gestational trophoblastic disease in androgenetic moles and the morphological features associated with low risk postmolar gestational trophoblastic disease2010

    • Author(s)
      Kaneki, E., Kobayashi, H., et al
    • Journal Title

      Cancer Sci

      Volume: 101 Pages: 1717-1721

    • NAID

      10026595031

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The level of RCAS1 expression is inversely correlated with the number of vitamin-positive stromal cells in epithelialovarian cancer2009

    • Author(s)
      Sonoda, K, Miyamoto S, Kobayashi H, Ogawa S, Okugawa K, Taniguchi S, Wake N
    • Journal Title

      Int J Gynecol Cancer

      Volume: 19(5) Pages: 838-843

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Feasibility study of neoadjuvant chemotherapy followed by interval debulking surgery for stage III/IV ovarian, tubal, and peritoneal cancers : Japan Clinical Oncology Group Study JCOG02062009

    • Author(s)
      Onda, T., Kobayashi, H., et al
    • Journal Title

      Gynecologic Oncology 113

      Pages: 57-62

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical characterization of mullerian mucinous borderline tumors : possible histogenetic link with serous borderline tumors and low-grade endometrioid tumors2009

    • Author(s)
      Yasunaga, M., Kobayashi, H., et al
    • Journal Title

      Human Pathology 40

      Pages: 965-974

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Level of RCAS1 Expression Is Inversely Correlated With the Number of Vitamin-Positive Stromal Cells in Epithelial Ovarian Cancer2009

    • Author(s)
      Sonoda, K., Kobayashi, H., et al
    • Journal Title

      International Journal of Gynecological Cancer 19

      Pages: 838-843

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Prognosis and postsurgical complications of 78 cervical cancer patients who received abdominal radical or simple treachelectomy in our hospital during these 6 years2011

    • Author(s)
      H.Kobayashi, K.Okugawa, H.Yahata, K.Sonoda, N.Wake
    • Organizer
      2^<nd> Biennial Meeting of Asian Society of Gynecologic Oncology
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2011-11-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Sentinel node detection with (99m)Tc phytate alone is satisfactory for cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy2011

    • Author(s)
      H.Yahata, H.Kobayashi, S.Ogawa, K.Okugawa, K.Sonoda, N.Wake
    • Organizer
      2^<nd> Biennial Meeting of Asian Society of Gynecologic Oncology
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2011-11-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] プラチナ感受性再発卵巣がんに対する、標準的化学療法は?~プラチナ感受性再発卵巣がんに対する臨床の実際~2011

    • Author(s)
      小林裕明
    • Organizer
      第49回日本癌治療学会(招請講演)
    • Place of Presentation
      名古屋市
    • Year and Date
      2011-10-28
    • Related Report
      2011 Final Research Report
  • [Presentation] 腹式子宮頸部摘出術後に分娩した頸癌2症例の比較:吻合部周囲静脈瘤の経緯に着目して2011

    • Author(s)
      小林裕明
    • Organizer
      第49回日本癌治療学会
    • Place of Presentation
      名古屋市
    • Year and Date
      2011-10-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] プラチナ感受性再発卵巣がんに対する、標準的化学療法は?プラチナ感受性再発卵巣がんに対する臨床の実際2011

    • Author(s)
      小林裕明
    • Organizer
      第49回日本癌治療学会
    • Place of Presentation
      名古屋市(招待講演)
    • Year and Date
      2011-10-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] 若い女性に増えてきた子宮頸がん:妊孕性温存手術としての腹式子宮頸部摘出術について2011

    • Author(s)
      小林裕明
    • Organizer
      周南産婦人科フォーラム
    • Place of Presentation
      周南市(招待講演)
    • Year and Date
      2011-10-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] Metronomic chemotherapy理論に基づくがん休眠療法と術後補助療法2011

    • Author(s)
      小林裕明
    • Organizer
      第4回北摂骨盤底疾患研究会(特別講演)
    • Place of Presentation
      大阪市
    • Year and Date
      2011-09-10
    • Related Report
      2011 Final Research Report
  • [Presentation] Metronomic chemotherapy理論に基づくがん休眠療法と術後補助療法2011

    • Author(s)
      小林裕明
    • Organizer
      第4回北摂骨盤底疾患研究会
    • Place of Presentation
      大阪市(招待講演)
    • Year and Date
      2011-09-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] 子宮頸がんに対する妊孕性温存手術としての腹式子宮頸部摘出術:予後と妊娠・分娩について2011

    • Author(s)
      小林裕明
    • Organizer
      第28回筑豊婦人科腫瘍懇話会
    • Place of Presentation
      飯塚市(招待講演)
    • Year and Date
      2011-09-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] 子宮肉腫の診断と治療~鑑別診断の難しさと治療ガイドライン作成の困難~2011

    • Author(s)
      小林裕明
    • Organizer
      第18回中四国GnRH研究会
    • Place of Presentation
      高松市(招待講演)
    • Year and Date
      2011-08-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] 妊娠帰結と同時に広汎子宮頸部摘出術を行った頸癌症例より考察するin utero trachelectomyの留意点2011

    • Author(s)
      小林裕明, 奥川馨, 井上貴史, 兼城英輔, 矢幡秀昭, 園田顕三, 加耒恒壽, 和氣徳夫
    • Organizer
      第50回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      札幌市
    • Year and Date
      2011-07-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] 婦人科がん治療における最近の話題:再発卵巣がんに対するDoxilの登場と子宮頸癌に対するトラケレクトミー2011

    • Author(s)
      小林裕明
    • Organizer
      京滋卵巣がん化学療法学術講演会
    • Place of Presentation
      京都市(招待講演)
    • Year and Date
      2011-07-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] Metronomic chemotherapy理論に基づくがん休眠療法と維持化学療法2011

    • Author(s)
      小林裕明
    • Organizer
      第24回関越DIF研究会(特別講演)
    • Place of Presentation
      東京
    • Year and Date
      2011-02-19
    • Related Report
      2011 Final Research Report
  • [Presentation] Metronomic chemotherapy理論に基づくがん休眠療法と維持化学療法2011

    • Author(s)
      小林裕明
    • Organizer
      第24回関越DIF研究会
    • Place of Presentation
      東京都(特別講演)
    • Year and Date
      2011-02-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 難治性再発の子宮頸がんおよび卵巣がんに対するイリノテカンのエビデンスとトライアル2010

    • Author(s)
      小林裕明
    • Organizer
      第49回日本婦人科腫瘍学会学術講演会(招請講演)
    • Place of Presentation
      佐賀
    • Year and Date
      2010-12-04
    • Related Report
      2011 Final Research Report
  • [Presentation] 難治性再発卵巣がんに対するがん休眠状態を目指したテーラード化学療法の基礎的臨床的研究2010

    • Author(s)
      小林裕明
    • Organizer
      第49回日本婦人科腫瘍学会学術講演会(公募研究助成報告)
    • Place of Presentation
      佐賀
    • Year and Date
      2010-12-04
    • Related Report
      2011 Final Research Report
  • [Presentation] シンポジウム:難治性再発卵巣癌に対する治療:病巣の進行を抑制し共存延命を目指すがん休眠化学療法2010

    • Author(s)
      小林裕明
    • Organizer
      第47回日本癌治療学会学術集会
    • Place of Presentation
      横浜市
    • Year and Date
      2010-10-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] Metronomic Chemotherapy理論に基づく術後補助療法の有用性2010

    • Author(s)
      小林裕明
    • Organizer
      第4回北関東婦人科がん臨床試験コンソーシアム教育セミナー(招請講演)
    • Place of Presentation
      浦和市
    • Year and Date
      2010-05-13
    • Related Report
      2011 Final Research Report
  • [Presentation] 卵巣癌治療の新たな展開-10年後を見据えて-難治性再発卵巣癌に対する治療:病巣の進行を抑制し共存延命を目指すがん休眠化学療法2009

    • Author(s)
      小林裕明
    • Organizer
      第47回日本癌治療学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-24
    • Related Report
      2011 Final Research Report
  • [Book] Diagnosis and treatment handbook of ovarian cancer (卵巣癌診療ハンドブック)2009

    • Author(s)
      谷口秀一, 小林裕明
    • Total Pages
      400
    • Publisher
      ヴァン メディカル
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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