Evaluation of ventricular function by echocardiography and radionuclide angiography in patients treated with...

Mitoxantrone, an anthracenedione derivative structurally similar to anthracycline, was tested in 25 Phase II patients with advanced breast cancer, previously treated with different cycles of 5-fluorouracil. Cardiac toxicity was evaluated by means of electrocardiography, echocardiography and radionuclide left-ventricular ejection fraction. Ten patients received a cumulative dose less than 70 mg/m2 (median 33.6, range 28-63) and 15 a dose equal to or more than 70 mg/m2 (median 81, range 70-84). ECG abnormalities in the form of dysrhythmias and ST-T changes were observed in 41% of the patients. Echocardiographic myocardial function parameters recorded in 10 of the 15 patients who received more than 70 mg/m2 demonstrated a trend to deterioration, whereas the nuclear angiographic ejection fraction recorded in all 15 patients who had more than 70 mg/m2 had significantly decreased. No patients developed congestive heart failure but almost one-quarter of them had a fall in myocardial function parameters of more than 15% compared to pretreatment values. These data indicate that mitoxantrone has a significant toxic effect on myocardial cells also at cumulative doses of less than 85 mg/m2 which is generally considered beyond the limit of safety for patients without risk factors.