Prospective evaluation of chronic cardiotoxicity due to high-dose epirubicin or combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil.

In a prospective study the left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), systolic blood pressure, ECG, and heart rate were recorded at rest and during submaximal work to compare the cardiotoxic effect of epirubicin with a combination chemotherapy without known cardiotoxicity. A total of 14 females with advanced breast cancer were treated with epirubicin at a median cumulative dose of 827 mg/m2 (range, 550-1244). These patients had previously received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or cyclophosphamide alone as adjuvant treatment, or CMF for advanced disease. The control group consisted of 11 females with advanced breast cancer given CMF only. The systolic blood pressure at rest as well as during submaximal work was significantly lower (P less than 0.05) after treatment in the epirubicin group than in the CMF controls. With regard to LVEF, the median value of 54% at rest was significantly lower after treatment in the epirubicin group than in the controls (59%). There was a significant fall in LVEF at rest and during exercise in the epirubicin group, whereas no such changes were found in the CMF controls after treatment. The RVEF was unaffected. In the epirubicin-treated group one patient developed fatal congestive heart failure, and in the remaining 13 patients treatment was discontinued due to progression of the cancer and not to cardiotoxicity. Thus, the cardiotoxicity of epirubicin changed the clinical outcome in only 1 of 14 patients with advanced breast cancer.