TRIAL OF ICRF-187 TO DECREASE DOXORUBICIN CARDIOMYOPATHY

阿霉素引起的心肌病限制了累积剂量 这种药物可以给癌症患者使用。我们 建议进行一项随机临床试验，以测试 ICRF-187预防本病132例 晚期不能手术的乳腺癌患者将是 接受以阿霉素为基础的细胞毒药物组合。 之所以选择ICRF-187是因为在广泛的动物研究中 始终如一地预防慢性阻塞性肺疾病的病理变化 阿霉素心肌病。该药物还在美国进行了测试 人类正在进行临床试验，并已被证明是无毒的 为这项研究建议的剂量。所有患者将获得5- 氟尿嘧啶、阿霉素和环磷酰胺，并将 随机接受ICRF-187。ICRF将作为一项 阿霉素注射前30分钟静脉推注。 将对患者进行急性毒性监测 经临床检查的化疗药物，血液 检查和X光检查。 这项研究的主要目的是发展 心脏毒性将通过临床检查进行评估， 静息和静息测定的左心室射血分数 运动核门池扫描和病理改变见于 右室心内膜心肌活检。会做活组织检查 36例患者中。 这项研究开始了，收集了87名患者的初步结果 显示出统计上显著的心脏保护措施 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意义 时间到了。该药的非心脏毒性和抗肿瘤作用 组合不是通过在此添加ICRF-187来选举的 剂量和时间表。 这项建议是为了完成注资的原有应计项目和 完成数据分析。

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.