TRIAL OF ICRF-187 TO DECREASE DOXORUBICIN CARDIOMYOPATHY

ICRF-187 减少阿霉素心肌病的试验

• 批准号: 3174152
• 负责人: JAMES SPEYER
• 金额: $ 13.08万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3174152
• 关键词: biopsy; breast neoplasms; cardiotonic agents; clinical trials; combination chemotherapy; cyclophosphamide; doxorubicin; drug adverse effect; fluorouracil; human subject; human therapy evaluation; myocardium disorder; neoplasm /cancer chemotherapy

Doxorubicin induced cardiomyopathy limits the cumulative dose of this drug which can be administered to cancer patients. We propose a randomized clinical trial to test the effectiveness of the agent ICRF-187 in preventig this cardiomyopathy in 132 patients with advanced inoperable breat cancer who will be receiving a doxorubicin based combination of cytotoxic drugs. ICRF-187 was chosen because in extensive animal studies it consistently prevented the pathologic changes of chronic doxorubicin cardiomyopathy. The drug has also been tested in humans in clinical trials and has been shown to be non-toxic in the doses proposed for this study. All patients will receive 5- fluorouracil, doxorubicin, and cyclophosphamide and will be randomized to receive ICRF-187. The ICRF will be given as an I.V. bolus 30 minutes prior to the administrations of doxorubicin. Patients will be monitored for acute toxicity to the chemotherapeutic agents by clinical examination, blood examinations and x-rays. The primary endpoint of the study is the development of cardiotoxicity which will be assessed by clinical examination, falls in left ventricular ejection fractions as measured by resting and exercise nucler gated pool scans and pathologic changes seen in right ventricular endomyocardial biopsies. Biopsies will be done in 36 patients. The study was started and accrued 87 patients preliminary results indicated statistically significant cardiac protection as measured by nuclear gated pool scans. Clinical and biopsy data all suggest cardiac protection but are not statistically significant at this time. Non cardiac toxicity and antitumor efficacy of the drug combination are not elected by the addition of ICRF-187 in this dose and schedule. This proposal is to complete the original accrual of injection and complete data analysis.

阿霉素诱导的心肌病限制了累积剂量 这种药物可以用于癌症患者。 我们 提出一项随机临床试验，以测试 ICRF-187预防132例心肌病 晚期无法手术的乳腺癌患者， 接受基于阿霉素的细胞毒性药物组合。 选择ICRF-187是因为在广泛的动物研究中， 持续预防慢性炎症的病理变化， 阿霉素心肌病 该药物还在美国进行了测试。 在临床试验中被证明是无毒的， 本研究建议的剂量。 所有患者将接受5- 氟尿嘧啶、阿霉素和环磷酰胺， 随机接受ICRF-187。 ICRF将作为一个 在给予阿霉素前30分钟静脉推注。 将监测患者的急性毒性， 临床检查用化学治疗剂，血液 检查和X光。 研究的主要终点是 将通过临床检查评估的心脏毒性，福尔斯 通过静息测量左心室射血分数， 运动核门控池扫描和病理变化， 右心室肌内膜活检。 将进行活检 36例患者 研究开始并获得了87例患者的初步结果 表明测量的心脏保护具有统计学显著性 通过核门控池扫描 临床和活检数据都表明 心脏保护，但在这方面没有统计学意义。 时间 药物的非心脏毒性和抗肿瘤疗效 在本研究中，通过添加ICRF-187， 剂量和时间表。 本建议是为了完成原有的应计注入， 完整的数据分析。