Cardiotoxicity of epirubicin/paclitaxel-containing regimens: Role of cardiac risk factors

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 th e benefit of chemotherapy may be negated by the occurrence of congestive he art failure (CHF), Patients and Methods: A total of 105 patients who were referred for epirubi cin/paclitaxel treatment were included in this study. Treatment regimens we re as follows: (1)epirubicin 90 mg/m(2) plus paclitaxel 135 to 225 mg/m(2) over 3 hours (n = 76); and (2) gemcitabine 1,000 mg/m(2) on days 1 and 4 pl us epirubicin/paclitaxel (n = 29), The occurrence of CHF was detected by ph ysical examination, and left ventricular function was evaluated by bidimens ional echocardiography to support the diagnosis. Cardiac risk factors exami ned in this study included age, prior radiotherapy to the chest, hypertensi on, and diabetes, Results: No patient experienced CHF while on treatment. Nine patients (9%) developed CHF after cumulative epirubicin doses of 1,080 mg/m(2) (n = 4), 7 20 mg/m2 (n = 2), 630 mg/m(2) (n = 1), and 540 mg/m(2) (n = 2), One of the two patients who developed CHF after a cumulative epirubicin dose of 540 mg /m(2) had received consolidation with high-dose chemotherapy, Median rime t o appearance of cardiologic symptoms was 3 months after the end of treatmen t (range, 3 to 6 months), Overall, the incidence of CHF was 13% and 4% in p atients with or without cardiac risk factors, respectively. The cumulative risk of developing CHF wets estimated as 7.7% ata cumulative doses of 720 m g/m(2) and 48.7% at a cumulative dose of 1,080 mg/m(2). Conclusion: This study shows that the CHF after an epirubicin/paclitaxel re gimen is low up to cumulative epirubicin doses of 990 mg/m(2), thus allowin g the safe administration of this regimen even in patients who received epi rubicin in the adjuvant setting. However, the risk of developing CHF increa ses when a cumulative dose exceeding 990 mg/m(2) is reached, concomitantly with the presence of an additional car diac risk factor. (C) 1999 by Americ an Society of Clinical Oncology.