Risk factors for development of daunorubicin cardiotoxicity

Daunorubicin has been in clinical trials in the United States for the past 15 years. In 1966, Dr. David Karnofsky was the first investigator to report congestive heart failure in patients who had received high doses of daunorubicin. This early report was followed by a study by Halazun et al, colleagues who carried out a randomized controlled trial of vincristine plus prednisone versus vincristine plus prednisone plus daunorubicin. They reported a 0% incidence of congestive heart failure in the two-drug regimen and a 9.99% incidence in the three-drug regimen containing daunorubicin. Since that report there have been a large number of reports in the literature documenting that congestive heart failure can occur with administration of daunorubicin. Unfortunately, even though the drug-induced cardiotoxicity is a well-documented phenomenon, there has been very little information available as regards its incidence or risk factors for its development. This is in contrast to Adriamycin, where both the incidence of and risk factors for the development of cardiotoxicity are better studied. Because of this paucity of information we began a large retrospective study in 1976 to determine the incidence of and risk factors for the development of daunorubicin-induced cardiotoxicity. The incidence data have been reported previously. This communication will review the incidence data and report new findings on the risk factors.