EPIRUBICIN CARDIOTOXICITY - AN ANALYSIS OF 469 PATIENTS WITH METASTATIC BREAST-CANCER

Purpose: To evaluate the influence of cumulative dose, dose-intensity, single-dose level, and schedule of epirubicin on the risk of developi ng congestive heart failure (CHF) in patients with advanced breast can cer. Patients and Methods: Four hundred sixty-nine consecutive anthrac yline-naive patients with metastatic breast cancer were included. Only patients with cardiac failure according to New York Heart Association (NYHA) function class II or more were recorded as having CHF, For eac h patient, the following were calculated: the cumulative dose of epiru bicin, mean dose-intensity (cumulative dose of epirubicin/duration of treatment), and single-dose level (cumulative dose of epirubicin/numbe r of injections). Results: Thirty-four patients (7.2%) developed CHF, The cumulative risk of cardiotoxicity was 4% at 900 mg/m(2) and increa sed exponentially to 15% at 1,000 mg/m(2). Irradiation against the med iastinum and thoracic spine increased the risk of CHF (P = .025), but dose-intensity, single-dose level, and schedule had no influence on th e risk of developing CHF, Age, previous adjuvant irradiation (to the l eft or right hemithorax), and previous chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF]) were not risk factors. The medi an rime to onset of CHF following the last dose of epirubicin was 57 d ays (range, 0 to 853), Among patients with CHF, 13 (38.2%) died of car diac failure. The median survival time for all patients with CHF was 1 62 days (range, 0 to + 1,957), Previous irradiation directly against t he heart increased the risk of death due to cardiac failure and decrea sed the median survival time to 125 days (range, 0 to 336), Conclusion : The present large retrospective study of 469 patients substantiates previous results concerning the cardiotoxicity of epirubicin. A signif icantly increasing risk of CHF in patients who receive cumulative dose s greater than 950 mg/m(2) was established. The future recommended max imum cumulative dose of epirubicin should be 900 mg/m(2) in patients w ith metastatic breast cancer. Previous irradiation against the heart l eads to an increased risk of developing CHF with an accelerated course to death, which indicates an additive cardiotoxic effect of irradiati on and epirubicin. (C) 1998 by American Society of Clinical Oncology.