Optimal Chemotherapy for High-Risk Early-Stage Breast Cancer

TO THE EDITOR: Burnell et al show that doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) is significantly inferior to cyclophosphamide, epirubicin, and fluorouracil (CEF) or dose-dense epirubicin and cyclophosphamide followed by paclitaxel (EC/T) in terms of relapse-free survival in node-positive and high-risk node-negative breast cancer. However, the toxicities of the regimens are quite different: AC/T had a febrile neutropenia rate of only 4.8%, whereas the rates for CEF and EC/T were 22.3% and 16.4%, respectively. Using the lower limits of the CIs calculated by the authors, we may determine that that the absolute improvement in relapse-free survival with the more aggressive regimens may be no more than 1% to 2% (the maximum benefit being 10% to 12%). To determine whether the excess toxicity is worthwhile, it would be helpful to know if it is modifiable. Of course, all patients treated with dose-dense EC/T received filgrastim, but the authors note that filgrastim use was permitted, not mandated, with CEF. Could the authors provide information on the percentage of patients treated with CEF who received filgrastim, as well as its effect on febrile neutropenia? If this was relatively low, the abrogation of febrile neutropenia by the routine addition of filgrastim or pegfilgrastim could make CEF the optimal regimen in this patient population. Carl D. Atkins New York Oncology Hematology Associates, Hudson, NY