[Doxorubicin-induced cardiomyopathy: hemodynamic studies for evaluating the limit of therapeutic risk]

To evaluate the therapeutic risk of doxorubicin therapy in terms of drug-induced cardiomyopathy, 75 female patients with metastasizing breast cancer (mean age: 60 +/- 7 years) were submitted to right heart catheterization at rest and on exercise: 37 of these patients underwent postoperative adjuvant radiotherapy; 38 patients were not pretreated. The hemodynamic profile of these patients was compared to that of eight healthy volunteers. Prior to doxorubicin therapy irradiated patients showed myocardial dysfunction characterized by significantly elevated pulmonary wedge pressures (PCP) on exercise (p less than 0.005). In the course of doxorubicin therapy a significant decrease in myocardial function could be observed at 500 mg/m2 cumulative dose in irradiated patients (p less than 0.05) and at 600 mg/m2 in non-irradiated patients (p less than 0.001). According to the hemodynamic classification of Reindell and Roskamm, after reaching a cumulative doxorubicin dose of less than 300 mg/m2, previously irradiated breast cancer patients showed a risk of developing stage III heart failure equal to that shown by nonirradiated patients after 400-500 mg/m2. It may be concluded that adjuvant radiotherapy can produce myocardial damage. Irradiated patients show a higher risk of developing doxorubicin-induced cardiomyopathy than nonirradiated patients. The limit of therapeutic risk should be established at stage III heart failure because cardiac failure can still be improved by treatment involving glycosides and a vasodilator.