The impact of epoetin-alpha on anemia, red blood cell (RBC) transfusions, and survival in breast cancer patients (pts) treated with dose-dense sequential chemotherapy: Mature results of an AGO phase III study (ETC trial)

Abstract

569 Background: Dose-dense chemotherapy has been shown to have a significant advantage in disease-free survival (DFS) and overall survival (OS) in high risk breast cancer pts, but leads to a higher number of RBC transfusions (CALGB C9741, AGO-ETC). Controversial results have been reported regarding the influence of Epoetin-alpha on DFS and OS in cancer pts. Methods: From 12/98 until 4/03, 1,284 pts were recruited into a multi-center phase-III trial. Breast cancer pts with at least 4 involved lymph nodes and below 65 years of age were randomized between a standard regimen (4 × EC followed by 4 × Paclitaxel) and a dose-dense arm consisting of three courses each of epirubicin (150 mg/m2), paclitaxel (225 mg/m2) and cyclophosphamide (2,500 mg/m2) at 2 weeks interval (ETC). A second randomization ± Epoetin-alpha was performed in the ETC arm only (150 IU/kg/sc three times weekly). Results: In 10/06, 1255 (98%) pts were evaluable. 658 pts were randomized in the dose-dense ETC arm, of whom 333 received Epoetin-alpha. Median follow- up is 62 months. Anemia was seen significantly more often in the ETC-arm alone compared to treatment with Epoetin-alpha (p<0.0001). Altogether, 11% of all patients were treated with RBC transfusions. Standard EC->T treatment resulted in 1% RBC transfusions, but 28% in the ETC arm alone vs. 13% in the ETC + Epoetin-alpha-arm (p<0.0001) received RBC transfusions. Despite this significantly higher transfusion rate the median Hb-value dropped from 12,8g/dl at cycle 1 to 10,7g/dl at cycle 9 in the ETC arm alone. In contrast the same value remained stable with Epoetin-alpha (12,4g/dl at cycle 1 and 9 each). At a median follow-up of 62 months, there is no difference between the ETC-arm alone and the ETC + Epoetin-alpha-arm concerning 5-year DFS and OS ((71% vs. 72% (p=0.86) and 83% vs. 81% (p=0.89)). Conclusions: The dose-dense adjuvant ETC-regimen significantly improves DFS and OS but is combined with relevant hematological toxicity. Epoetin-alpha significantly reduces the number of RBC transfusions and prevents anemia. However, the prevention of anemia has no influence on DFS and OS in the adjuvant treatment with dose-dense ETC. [Table: see text]