LATE CARDIAC TOXICITY OF DOXORUBICIN, EPIRUBICIN, AND MITOXANTRONE THERAPY FOR HODGKINS-DISEASE IN ADULTS

Cardiotoxicity is a well recognized side effect of anthracyclines (doxorubicin and epirubicin) or antracenadiones (mitoxantrone) at cumulative or high doses. However the side effects have not been evaluated in adults with Hodgkin's disease who received therapeutic doses of these drugs. We analyzed the cardiac function studying the left ventricular ejection fraction (LVEF) at rest in 136 patients with Hodgkin's disease treated with doxorubicin, epirubicin or mitoxantrone used in combination with vinblastine, bleomycin and decarbazine. No other risk factors, such as radiation therapy to the mediastinum, were considered. The follow-up is 5 to 8 years for patients in complete remission. Forty-five patients received doxorubicin (from 325 to 685 mg/m2, median 475 mg/m2), 51 patients received epirubicin (from 310 to 610 mg/m2, median 510 mg/m2) and 40 patients were treated with mitoxantrone (from 70 to 165, median 125 mg/m2). The median time between the end of treatment and the evaluation was 6.7 years. Thirty seven percent of the patients (similar rates in the three groups) showed abnormalities in the LVEF with decreased rates independent of the drug dosage. These were compared with two control groups, 46 patients treated with the MOPP combination (mechlorethamine, vincristine, prednisone and procarbazine) or LOPP (chlorambucil, for mechlorethamine) and 35 healthy volunteers. We believe that the use of anthracyclines or antracenadione will produce late cardiac effects in a fraction of patients independently of the doses used and that the indications for these drugs be carefully monitoring so as to evaluate the development of late side effects.