Abstract P3-15-09: Symptomatic Congestive Heart Failure after Neo/Adjuvant Dose-Dense Epirubicin: A Retrospective Analysis of Two Trials with Long-Term Follow-Up

Abstract

Abstract Background: Dose-dense (dd) anthracycline-taxane (A/T) based regimens (Rxs) have led to incremental benefits in breast cancer outcomes. Long-term incidence of symptomatic cardiac events for A/T Rxs (conventional and dd) has been ≥2.5%. The risk of long-term cardiac dysfunction related to total anthracycline dose and schedule remains a clinical concern. Additionally, the significance of asymptomatic short-term changes in left ventricular ejection fraction (LVEF) on the development of clinically significant congestive heart failure (CHF) is uncertain. Here we examine the incidence of symptomatic CHF, as per the New York Heart Association (NYHA) functional classification, for 82 patients (pts) exposed to neo/adjuvant dd epirubicin. Methods: We conducted a retrospective review of pts treated on two clinical trials: trial A-pts received fluorouracil, epirubicin, and cyclophosphamide (FEC) (500/100/500 mg/m2 every 2 weeks x 6) followed by weekly paclitaxel (80 mg/m2) alternating with docetaxel (35 mg/m2) x18; trial B-pts received EC (100/600 mg/m2 every 2 weeks x 6) followed by paclitaxel (175 mg/m2 every 2 weeks x 6). Total E dose was 600 mg/m2 for each trial. Pts with a known history of unstable angina, myocardial infarction, and/or CHF were excluded. All pts received a baseline LVEF evaluation, and in trial B pts received a repeat evaluation within 3 months after Rx completion. Results: Trial A enrolled 44 pts with a median age of 46 years (range, 26-63), 9 pts with pre-existing diagnosis of hypertension (HTN), and a median baseline LVEF of 66% (55-80%); 16/44 (36%) pts received left-sided radiation. At a median follow-up of 83 months, one patient (2.2%) developed NYHA class III CHF; 12 months after Rx completion her repeat LVEF was stable and 75 months after completion, an echocardiogram showed an LVEF of 21%. Trial B enrolled 38 pts with a median age of 47 years (30-72), 5 pts with pre-existing HTN, and a median baseline LVEF of 69% (57-85%); 18/38 (47%) pts received left-sided radiation. Within 3 months of Rx completion, 28/38 (74%) pts had a repeat LVEF assessment with a median LVEF of 65% (40-76%). At a median follow-up of 56 months, one patient (2.6%) developed anthracycline-induced symptomatic class II CHF three months after Rx completion (baseline LVEF 61%, 3 months LVEF 42%). One patient (2.6%) suffered class III CHF one week after completing Rx with LVEF of 40%; this was in the setting of cocaine use and a repeat LVEF evaluation one month after the event showed a return to baseline LVEF. Overall, 2/82 (2.4%) pts had NYHA class III CHF. Conclusion: With long term follow-up our two studies demonstrate an acceptable 2.4% incidence of NYHA class III CHF after dose-dense epirubicin therapy. These findings are consistent with those of larger randomized trials evaluating the anthracyclines in breast cancer treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-15-09.