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

“节拍化疗”治疗妇科肿瘤的疗效研究

• 批准号: 21592135
• 负责人: KOBAYASHI Hiroaki
• 金额: $ 3.16万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592135/
• 关键词: 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

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.

最近提出的“节拍化疗”是一种新的治疗方法，基于血管内皮细胞对即使是少量药物也可重复敏感的背景，使用重复施用低剂量抗癌药物来诱导“肿瘤休眠状态”，即使是耐药肿瘤也没有严重的副作用。本研究通过动物实验和临床试验来评价节拍化疗对妇科恶性肿瘤的疗效。采用分次低剂量或单次高剂量紫杉醇治疗人卵巢癌紫杉醇耐药瘤小鼠，前者对肿瘤生长抑制作用更强。分低剂量给药对小鼠的毒性明显较轻。因此，节拍化疗似乎能够抑制肿瘤生长，尽管对耐药肿瘤有轻微的副作用。因此，通过评价Matrigel中的新生血管形成的实验，发现分次低剂量施用紫杉醇比单次高剂量施用更好地抑制新生血管形成。其他抗癌药物多西他赛和伊立替康也获得了类似的结果。基于节拍化疗的理论，我们进行了一项肿瘤休眠治疗的临床试验，即采用个体化最大重复剂量（iMRD）的分次低剂量抗癌药物给药。经IRB批准至今，42例卵巢癌和29例宫颈癌难治性复发病例被引入本研究，获得了良好的生活质量和相对较长的TTP（进展时间）。尽管病例数少，随访时间短，但节拍化疗应用于肿瘤休眠治疗的疗效仍值得肯定。

项目成果

Cytoplasmic and stromal expression of laminin 2 chain correlates with infiltrative invasion in ovarian mucinous neoplasms of gastro-intestinal type

层粘连蛋白2链的细胞质和基质表达与胃肠道型卵巢粘液性肿瘤的浸润性侵袭相关

• 发表时间: 2011
• 期刊: Oncol Rep
• 影响因子: 4.2
• 作者: Okuma E;Ohishi Y;Oda Y;Aishima S;Kurihara S;Nishimural;Yasunaga M;Kobayashi H;Wake N;Tsuneyoshi M
• 通讯作者: Tsuneyoshi M

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

卵巢癌治疗新进展 - 展望10年 - 难治性和复发性卵巢癌的治疗：旨在抑制疾病进展和延长共存生存期的癌症休眠化疗

• 发表时间: 2009
• 作者: 岩元一朗;堂地勉;小林裕明
• 通讯作者: 小林裕明

Feasibility study of neoadjuvant chemotherapy followed by interval debulking surgery for stage III/IV ovarian, tubal, and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0206

• DOI: 10.1016/j.ygyno.2008.12.027
• 发表时间: 2009-04-01
• 期刊: GYNECOLOGIC ONCOLOGY
• 影响因子: 4.7
• 作者: Onda, Takashi;Kobayashi, Hiroaki;Yoshikawa, Hiroyuki
• 通讯作者: Yoshikawa, Hiroyuki

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

伊立替康治疗难治性和复发性宫颈癌和卵巢癌的证据和试验

• 发表时间: 2010
• 作者: 齋藤文誉;田代浩徳;大竹秀幸;大場隆;片渕秀隆;小林裕明
• 通讯作者: 小林裕明

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

经腹宫颈切除术后两例宫颈癌分娩情况的比较：关注吻合口周围静脉曲张病史

• 发表时间: 2011
• 作者: Nagase S;Katabuchi H;Hiura M;Sakuragi N;Aoki Y;Kigawa J;Saito T;Hachisuga T;Ito K;Uno T;Katsumata S;Susumu N;Emoto M;Kobayashi H;Metoki H;Konishi I;Ochiai K;Mikami M;Sugiyama T;Mukai M;Sagae S;Hoshiai H;Aoki D;Ohmiri M;Yoshikawa H;小林裕明
• 通讯作者: 小林裕明