Second line chemotherapy for relapsed ovarian canser

复发性卵巢癌的二线化疗

• 批准号: 11671662
• 负责人: SUGIYAMA Toru
• 金额: $ 1.79万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671662/
• 关键词: ovarian cancer; chemotherapy; paclitaxel; CPT-11; cytotoxic effect; drug resistance; molecular biclogy

1.Experimental Chemotherapy : Sequential therapy with carboplatin, paclitaxel, and CPT-11 was performed for rat primary ovarian cancer. No macroscopic differences.in anti-tumor effects were observed, suggesting limitations of this sequential therapy in treatment of clinical cases, although some issues, such as selection of adequate doses, remain to be further investigated.2.Jnhibitory effect of an anti-vascularization inhibitor on tumor viability : Although an anti-vascularization inhibitor (FNP-470)was administered to rat neonates 7 days after intraperitoneal administration of DMBA-OC-1 (cell line), tumor viability did not differ between the control group (25/31, 80.6%) and the TNP-470-treated group (26/36, 72.2 %). The number of new blood vessels was identical between the two groups at microangiography. This experimental model was thought to correspond to clinical micro-residual cases. However, use of some concomitant drug(s) with TNP-470 seemd to be required, because it was suggested that TNP-470 bad difficulty in inhibiting vascularization when used, alone.3.Clinical Study : The response rate of CPT-11/CDDP was 40% (33% for patients with resistant disease). Activity of topoisomerase-1 significantly increased in the responding cases, compared with the non-responding cases, indicating a possibility that treatment can be performed using this activity as a target. Paclitaxel showed low toxicity and effectiveness when administered weekly (sensitive : 3/4, resistant : 1/6).. No responding cases with resistant disease were observed in the treatment with dcetaxel/CPT-11.Four often cases with sensitive disease (40%) responded to docetaxel/carboplatin. In 11 of 24 frozen-stored clinical specimens (45.8%), p53 mutation was detected. Thus this mutation has been continuously studied at the present time, in relation tq clinical efficacy. Because all. 24 cases examined were negative for c-erbB-2, indications of herceptin were thought to be very limited.

1.实验性化疗：采用卡铂、紫杉醇和CPT-11序贯治疗大鼠原发性卵巢癌。没有观察到肉眼differences.in的抗肿瘤作用，表明这种序贯疗法在治疗临床病例中的局限性，尽管一些问题，如选择适当的剂量，仍有待进一步研究。2.抗血管形成抑制剂对肿瘤活力的抑制作用：尽管在腹膜内施用DMBA-OC-1后7天向新生大鼠施用抗血管形成抑制剂（FNP-470），在TNP-470（细胞系）中，对照组（25/31，80.6%）和TNP-470处理组（26/36，72.2%）之间的肿瘤存活率没有差异。在微血管造影术中，两组之间的新生血管数量相同。认为该实验模型符合临床微量残留病例。临床研究：CPT-11/CDDP有效率为40%（耐药组为33%），与TNP-470合用时，TNP-470对血管生成的抑制作用较弱。与无应答病例相比，应答病例中拓扑异构酶-1的活性显著增加，表明可以使用该活性作为靶点进行治疗的可能性。紫杉醇每周给药时显示低毒性和有效性（敏感：3/4，耐药：1/6）。对多西他赛/卡铂治疗敏感性疾病4例（40%）有反应。在24例临床标本中，11例（45.8%）检测到p53突变。因此，目前已持续研究该突变与临床疗效的关系。因为所有。24例c-erbB-2阴性，赫赛汀的适应症有限。

项目成果

Kigawa J, Takahashi M, Minagawa Y.Oishi T.Sugiyama T, Yakushiji M, Terakawa N: "Topoisomerase I activity and response to second-line chemotherapy consisting of camptothecin and cisplatin in patients with ovarian cancer"International Journal of Cancer. 84.

Kikawa J、Takahashi M、Minakawa Y.Oishi T.Sugiyama T、Yakushiji M、Terakawa N：“拓扑异构酶 I 活性以及卵巢癌患者对由喜树碱和顺铂组成的二线化疗的反应”国际癌症杂志。

Sugivama T. Yakushiji M, Noda K, Ikeda M, Tanaka K, Aoki Y, Hasegawa K, Nishimura R: "BMS-181339 Ovarian Cancer Study Group : Paclitaxel-cisplatin combination in advanced ovarian cancer : a phase H study"Internationa Journal of Cancer. Vol.5, No.2. 85-88

Sugivama T. Yakushiji M、Noda K、Ikeda M、Tanaka K、Aoki Y、Hasekawa K、Nishimura R：“BMS-181339 卵巢癌研究组：紫杉醇-顺铂组合治疗晚期卵巢癌：H 期研究”国际期刊

Sugiyama T, Yakushiji M, Noda K, Ikeda M, Tanaka K, Aoki Y, Hasegawa K, Nishimura R: "BMS-181339 Ovarian Cancer Study Group : Paclitaxel-cisplatin combination in advanced ovarian cancer : a phase II study"International Journal of Clinical Oncology. 5. 85-

Sugiyama T、Yakushiji M、Noda K、Ikeda M、Tanaka K、Aoki Y、Hasekawa K、Nishimura R：“BMS-181339 卵巢癌研究组：紫杉醇-顺铂组合治疗晚期卵巢癌：一项 II 期研究”国际期刊

S.Ota, T.Sugiyama, K.Komai, K.N.Hirai, T.Kumagai S, Ushijima, K., Nishida, T., Kamura T.: "Weekly 1 hour paclitaxel infusion in patients with recurrent gynecologic tumors : a pilot study"Jpnanese Journal of Clinical Oncology. 31. 395-398 (2001)

S.Ota、T.Sugiyama、K.Komai、K.N.Hirai、T.Kumagai S、Ushijima, K.、Nishida, T.、Kamura T.：“复发性妇科肿瘤患者每周输注 1 小时紫杉醇：一项试点研究

駒井幹, 杉山徹, 平井伸幸, 品川敦彦, 牛嶋公生, 西田敬, 嘉村敏治: "上皮性卵巣癌のsecond-line chemotherapy"Oncology & Chemotherapy. 17. 116-121 (2001)

Miki Komai、Toru Sugiyama、Nobuyuki Hirai、Atsuhiko Shinakawa、Kousei Ushijima、Takashi Nishida、Toshiharu Kamura：“上皮性卵巢癌的二线化疗”《肿瘤学与化疗》17. 116-121 (2001)。