Why the study?
Does limiting the cumulative dose of adriamycin to less than 550 mg/m2 prevent severe congestive heart failure in patients treated for advanced carcinoma?
Does limiting the cumulative dose of adriamycin to less than 550 mg/m2 prevent severe congestive heart failure in patients treated for advanced carcinoma?
Adriamycin induces a dose-dependent, severe, and often fatal diffuse myocardiopathy, with the risk of congestive heart failure increasing dramatically at cumulative doses above 550 mg/m2.
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Cumulative adriamycin >550 mg/m2 was associated with higher CHF risk; supports dose limitation but leaves open prospective confirmation.
The cardiotoxic effects of adriamycin were studied in 399 patients treated for far-advanced carcimma. Forty-five patients (11%) exhibited transient electrocardiographs changes. Eleven others developed severe congestive heart failure. Eight of these latter patients died within 3 weeks of the onset of the cardiac decompensation. The diffuse nature of this myocardiopathy was suggested by: 1. a conspicuous decrease in the QRS voltage on the electrocardiograms; 2. rapidly occurring cardiac dilatation and ventricular failure, and 3. refractoriness to inoiropic drugs and mechanical ventricular assistance. Postmortem examination of the hearts in two cases showed a striking decrease in the number of cardiac: muscle cells present, degeneration of the remaining myocardial cells, loss o contractile substance, mitochondrial swelling, and intramitochondrial dense inclusion bodies. Congestive heart failure occurred only once in the 366 patients who were treated with less than 550 mg/m2 of adriamycin (0.27%), but there were 10 cases of cardiac failure in the 33 patients who received more than 550 mg/m2 of this drug (30%). Therefore, until more direct means are established to prevent adriamycin-induced congestive heart failure, it is suggested that the total dose of adriamycin should be limited to less than 550 mg/m2 to permit safer use of this efficacious cancer chemotherapeutic agent.
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Lefrak et al. (1973) studied this question.
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