Cardiotoxicity of Epirubicin/Paclitaxel–Containing Regimens: Role of Cardiac Risk Factors

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Abstract
PURPOSE: To evaluate the incidence of clinically relevant cardiac toxicity after treatment with epirubicin/paclitaxel-containing regimens in patients with metastatic breast cancer and to identify high-risk patients in whom the benefit of chemotherapy may be negated by the occurrence of congestive heart failure (CHF). PATIENTS AND METHODS: A total of 105 patients who were referred for epirubicin/paclitaxel treatment were included in this study. Treatment regimens were as follows: (1) epirubicin 90 mg/m2 plus paclitaxel 135 to 225 mg/m2 over 3 hours (n = 76); and (2) gemcitabine 1,000 mg/m2 on days 1 and 4 plus epirubicin/paclitaxel (n = 29). The occurrence of CHF was detected by physical examination, and left ventricular function was evaluated by bidimensional echocardiography to support the diagnosis. Cardiac risk factors examined in this study included age, prior radiotherapy to the chest, hypertension, and diabetes. RESULTS: No patient experienced CHF while on treatment. Nine patients (9%) developed CHF after cumulative epirubicin doses of 1,080 mg/m2 (n = 4), 720 mg/m2 (n = 2), 630 mg/m2 (n = 1), and 540 mg/m2 (n = 2). One of the two patients who developed CHF after a cumulative epirubicin dose of 540 mg/m2 had received consolidation with high-dose chemotherapy. Median time to appearance of cardiologic symptoms was 3 months after the end of treatment (range, 3 to 6 months). Overall, the incidence of CHF was 13% and 4% in patients with or without cardiac risk factors, respectively. The cumulative risk of developing CHF was estimated as 7.7% at a cumulative doses of 720 mg/m2 and 48.7% at a cumulative dose of 1,080 mg/m2. CONCLUSION: This study shows that the incidence of CHF after an epirubicin/paclitaxel regimen is low up to cumulative epirubicin doses of 990 mg/m2, thus allowing the safe administration of this regimen even in patients who received epirubicin in the adjuvant setting. However, the risk of developing CHF increases when a cumulative dose exceeding 990 mg/m2 is reached, concomitantly with the presence of an additional cardiac risk factor.