REDUCTION OF DOXORUBICIN CARDIOTOXICITY BY ICRF-187

阿霉素是一种抗癌的化疗药物。 恶性肿瘤。慢性阻塞性肺疾病最重要的剂量限制副作用 阿霉素治疗是一种心肌病。某些化合物可以修饰 阿霉素对动物的心脏毒性。在早期研究中，ICRF-159导致 显著降低柔红霉素的毒性。ICRF-187是水 ICRF-159的可溶性异构体与柔红霉素的心脏毒性 以及在兔子、仓鼠和狗身上使用阿霉素。取得了令人鼓舞的成果 在我们的实验室里，动物导致了对人类实验对象的初步研究。 组在30分钟前静脉注射ICRF-187 阿霉素似乎对心脏的非侵入性影响较小 功能测试比接受安慰剂的那一组要好。该计划的目的是 本研究旨在进一步评估ICR187量表对S的改善能力 阿霉素致心脏毒性。患者将被随机分配到 以双盲方式使用ICRF-187或安慰剂进行预处理。 基线评估将包括病史和身体检查，胸部 X光、心电图、收缩时间间期、超声心动图、核 血管造影术、全血计数、肝酶、肿瘤状态和 性能状态。血液检查、超声心动图和收缩时间 间隔时间将在随后的剂量之前重复 阿霉素。包括在以下位置执行的所有测试的总评估 当阿霉素累积剂量为300时，基线重复 500毫克/平方米。此外，心内膜心肌活组织检查将在 基线和累积剂量为300和500 mg/m2的受试者 同意。这两组患者将接受肿瘤反应评估。 以及两种药物方案的副作用。心脏功能研究将 用两种方法比较两组(每组45人) 方差分析。心内膜心肌活检将接受分级 (Billingham标准)和这两个组还将通过分析 差异。这项研究的成功完成应该证明 ICRF-187能否有效预防阿霉素诱导的心脏 功能和组织学改变。

Doxorubicin is a chemotherapeutic drug active against a variety of malignancies. The most important dose-limiting side effect of chronic doxorubicin treatment is cardiomyopathy. Certain compounds can modify doxorubicin cardiac toxicity in animals. In early studies, ICRF-159 caused a significant reduction of daunorubicin toxicity. ICRF-187 is the water soluble isomer of ICRF-159 and reduces the cardiac toxicity of daunorubicin and doxorubicin in rabbits, hamsters and dogs. The encouraging results in animals led to a preliminary study of human subjects in our laboratory. The group receiving bolus intravenous ICRF-187 30 minutes prior to doxorubicin appears to be having less change of cardiac non-invasive function tests than the group receiving placebo. The purpose of the present study is to further evaluate ICRF-187's ability to ameliorate doxorubicin induced cardiac toxicity. Patients will be randomized to pretreatment with either ICRF-187 or placebo in a double-blinded fashion. Baseline evaluation will include a history and physical examination, chest x-ray, electrocardiogram, systolic time intervals, echocardiograms, nuclear angiogram, complete blood count, liver enzymes, tumor status and performance status. Blood tests, the echocardiogram and systolic time intervals will be repeated immediately prior to subsequent doses of doxorubicin. A total evaluation including all the tests performed at baseline will be repeated when the cumulative doxorubicin dose is 300 and 500 mg/m2. In addition, an endomyocardial biopsy will be performed at baseline and at cumulative doses of 300 and 500 mg/m2 in those subjects who consent. The two groups of patients will be evaluated for tumor response and side effects to the two drug regimens. Cardiac function studies will be compared between the two groups (45 in each group) by the two way analysis of variance. The endomyocardial biopsy will receive a grade (Billingham criteria) and the groups will also be compared by analysis of variance. The successful completion of this study should demonstrate whether ICRF-187 effectively prevents doxorubicin-induced cardiac functional and histologic changes.