Severe and fatal anthracycline cardiotoxicity at cumulative doses below 400 mg/m2: evidence for enhanced toxicity with multiagent chemotherapy.

Three cases of severe, progressive, and in two cases, fetal cardiomyopathy secondary to anthracycline chemotherapy are reported. All of the patients were receiving multiagent chemotherapy for extremity sarcomas consisting of doxorubicin, high-dose methotrexate, bleomycin, cyclophosphamide, dactinomycin, and cisplatinum at the onset of their congestive heart failure. Cardiomyopathy developed in each patient at cumulative anthracycline doses less than 400 mg/m2. These cases suggest that enhanced cardiotoxicity may occur when anthracyclines are used in combination with other agents such as cyclophosphamide, bleomycin, cisplatinum, and methotrexate and that cumulative anthracycline doses considered to be "safe" may need to be lowered in these circumstances.