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 myocardiopathy. Prenylamine (PNL), a calcium antagonistic drug, provided partial protection against ADM-induced cardiotoxicity in mice and in the rabbit. Thus, it was considered important to evaluate the cardioprotective potential of PNL in patients given ordinary doses of ADM. Twenty-six patients were selected and randomized in two groups, and a double-blind trial was begun. Group A (n = 13): patients received ADM, i.v. at standard oncological doses up to 550 mg/m2, plus placebo, orally. Group B (n = 13): ADM was administered as in Group A, but PNL 200 mg/day was given instead of placebo. Standard ECG and chest radiographs were performed at the beginning of treatment and every two months. Mode-M echocardiograms and 24-hour ambulatory ECGs were obtained previously to the beginning of the ADM treatment and two months after the administration of the last dose of the drug. In Group A, three patients died from oncological causes, total ADM dose was 359 +/- 100 mg/m2, and the mean age was 59.7 years. One patient in this group developed a congestive myocardiopathy while another patient developed a severe supraventricular arrhythmia. In Group B, four patients died from oncological causes, total ADM dose was 367 +/- 132 mg/m2, and the mean age was 63.8 years. No myocardiopathy was found in this group. These findings suggest that simultaneous administration of PNL may mitigate ADM cardiotoxicity, but larger trials are needed to draw definite conclusions.

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, x 748 +/- 174 mg/m2; all noninvasive studies including RNV were normal. No correlation was found between 4'ADM 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 post-treatment (p less than 0.0001). Surprisingly, the post-exercise pretreatment ejection fraction also increased from 55.47 +/- 7.7% to 63.35 +/- 10% in post-treatment (p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)