ADRIAMYCIN CARDIOTOXICITY IN STAGE-IV BREAST-CANCER - POSSIBLE ENHANCEMENT WITH PRIOR LEFT CHEST RADIATION-THERAPY

Eighty Stage IV breast cancer patients treated with Adriamycin (doxorubicin hydrochloride) in clinical trials were evaluated for cardiotoxicity which was defined as either a significant but asymptomatic EKG change or an EKG change associated with heart failure. A comparison group consisted of 31 similar patients concurrently treated with chemotherapy exclusive of Adriamycin. Subgroupings of patients with either prior left chest radiation therapy or a pre-chemotherapy EKG abnormality were also examined. The frequency of an asymptomatic EKG change in the Adriamycin group was greater than twice (31.5-13%) the comparison group. These changes were more common in the setting of a pre-chemotherapy EKG abnormality and with prior left chest radiation therapy. Changes occurred independent of the total dose of Adriamycin to a maximum dose of 540 mg/m2. An asymptomatic EKG change was not an indication for stopping Adriamycin. Cardiotoxicity (expressed as heart failure) occurred in 3 Adriamycin treated patients. The Adriamycin dose was 420-490 mg/m2. All 3 patients had received prior left chest radiation therapy to 5000 rad. Post-mortem study showed diffuse fibrotic changes in the pericardium and myocardium with muscle fiber atrophy and nuclear swelling on light microscopy. Combination chemotherapy without Adriamycin did not appear to be clinically cardiotoxic. The lower threshold (420 mg/m2) for Adriamycin induced heart failure is thought to reflect enhanced or additive toxicity by prior heart irradiation. The interaction is recognized with an interval between radiation and Adriamycin up to 3 years in this study. Limiting the cumulative Adriamycin dose to 400 mg/m2 is recommended in patients who had previous left chest radiation to areas encompassing the heart. © 1979.