Hemodynamic effects of chronic 4′ epi-adriamycin administration

Summary

Adriamycin (ADM) is an effective antineoplastic drug. However, the amount of ADM that can be administered must be limited because of the risk of developing a severe dose-dependent cardiomyopathy. 4′Epi-adriamycin (4′ ADM) is a new anthracycline analog with similar antineoplastic properties as ADM, but with perhaps less cardiac toxicity. To determine myocardial performance after a chronic treatment with 4′ADM, we studied 17 patients (mean age 36.6 years) suffering from lymphomas by means of 24-hour ambulatory ECG, x-ray, M-mode echocardiogram, and rest-exercise gated radionuclide ventriculography (RNV), performed prior to and 2 months after the end of the treatment. Pretreatment and post-treatment shortening fractions, basal pretreatment and post-treatment ejection fractions, and postexercise pretreatment and post-treatment ejection fractions, were tested for correlation with individual 4′ADM doses and pretreatment with ADM. No association was noted among them, showing the lack of correlation between doses and impairment of ventricular performance. 4′ADM doses ranged from 400 to 1100,$\bar x$ 748±174 mg/m²; allnoninvasive studies including RNV doses and RNV (Pearson's correlation coefficient, p=ns). No deterioration of ventricular performance could be demonstrated. Conversely, the basal pretreatment ejection fraction changed from 56.17±7.6% to 61.52±8.3% in posttreatment (p<0.0001). Surprisingly, the postexercise pretreatment ejection fraction also increased from 55.47±7.7% to 63.35±10% in post-treatment (p<0.03). The shortening fraction changed from 35.47±4.8% to 36.47±4.2% after 4′ADM treatment (ns). No impairment of cardiac function could be shown in patients previously treated with ADM or radiotherapy. On the basis of these data, treatment with 4′ADM did not impair but improved cardiac function