Friedman M A, Bozdech M J, Billingham M E, Rider A K
JAMA. 1978 Oct 6;240(15):1603-6. doi: 10.1001/jama.240.15.1603.
Doxorubicin, whose dose-limiting toxicity is cardiomyopathy, was given to four cancer patients. Endomyocardial biopsy specimens and test results of cardiac function were obtained before, during, and after treatment. The biopsy specimens were examined by light and electron microscopy and were graded blindly. Evidence of specific doxorubicin injury was found in 3/4 patients with as little as 180 mg/sq m of the drug and became progressively more severe with higher doses. All test results of cardiac function, including systolic time intervals, remained normal. These data suggest that a specific, progressive subclinical injury to the heart occurs with doxorubicin therapy, which cannot be reliably detected by routine tests. This potential risk must be taken into account with the use of doxorubicin, especially when combined with synergistic agents.
对四位癌症患者使用了阿霉素，其剂量限制性毒性为心肌病。在治疗前、治疗期间和治疗后获取了心内膜活检标本及心脏功能测试结果。活检标本通过光学显微镜和电子显微镜进行检查，并进行盲法分级。在4例患者中有3例发现了特定的阿霉素损伤迹象，药物剂量低至180mg/平方米时就出现损伤，且随着剂量增加损伤逐渐加重。包括收缩期时间间期在内的所有心脏功能测试结果均保持正常。这些数据表明，阿霉素治疗会对心脏产生特定的、进行性的亚临床损伤，而常规测试无法可靠检测到这种损伤。在使用阿霉素时，尤其是与增效剂联合使用时，必须考虑到这种潜在风险。
