Cardiomyopathy after widely separated courses of adriamycin exacerbated by actinomycin-D and mithramycin

A 22-year-old man with a synovial cell sarcoma attained an excellent response to therapy with adriamycin (NSC-123127) and dimethyltriazeno imidazole carboxamide (NSC-45388). Therapy was discontinued at a cumulative dose of adriamycin of 600 mg/m2. Relapse occurred 13 1/2 months later, and therapy with adriamycin was restarted. Because of tumor progression, therapy was discontinued after a cumulative dose of adriamycin of 120 mg/m2. Ten weeks later, severe congestive heart failure developed which ultimately caused the patient's death. Exacerbations of the heart failure were temporally related to the administration of the antitumor antibiotics actinomycin-D (NSC-3053) and mithramycin (NSC-24559). Electron microscopic examination of the heart revealed changes characteristic of adriamycin cardiomyopathy. Thus, even after a long hiatus, it may not be safe to exceed the recommended maximum cumulative dose level of adriamycin. The pathogenic mechanisms involved in the development of adriamycin cardiomyopathy are reviewed, and the possible synergistic effect of other antitumor antibiotics is discussed.