NEAT-A: Accelerated sequential epirubicin followed by CMF using pegfilgrastim is a feasible regimen for delivering dose dense chemotherapy in early breast cancer

Abstract

11001 Background: E-CMF [epirubicin (E) x 4 cycles every (q) 21 days (d), followed by classical CMF x 4 cycles q 28d] is established as highly effective adjuvant chemotherapy for early breast cancer (BC), reducing mortality by 30% compared with CMF alone [Poole NEJM 2006]. However, dose dense anthracycline-taxane schedules, accelerated with GCSF support, have been shown to be superior to conventional regimens [Citron JCO 2003, Burnell SABCS 2006]. Exploration of accelerated E-CMF is therefore of considerable interest. Methods: A non-randomised, multicenter trial was designed to explore the feasibility and tolerability of accelerated E-CMF chemotherapy for women with early BC. The primary endpoint was delivered dose intensity (DDI). The accrual target was 40 patients (pts). Pts were treated with 4 cycles E (100mg/m2) q 14d, with Pegfilgrastim (PF) (6mg sc) d2, followed by 4 cycles of Cyclophosphamide, Methotrexate, and 5-Fluorouracil (600/40/600mg/m2) administered intravenously d1 + 8, with PF d9, q 21d. Results: 44 pts were enrolled. Complete dose information from 40 pts and toxicity data from 336 cycles (44 pts) has been analysed. Median DDI was 96.7% of target. Delays of >2 d were recorded for 8% of cycles. Dose reductions were recorded in 4% of cycles. 90% of pts received >85% intended total dose and 85% of pts received >85% intended DDI. Percentage grade 2 and 3/4 toxicity reported per cycle were respectively: fatigue 34/12; all infections 7/4; emesis 19/4; bone pain 18/4; diarrhoea 7/3; dyspnoea 20/3; febrile neutropenia not applicable (na)/2; mucositis 12/0.3; and phlebitis 29/na. Hospitalisation occurred in 10% of cycles. One pt developed endocarditis in association with repeated line infections, and a further pt experienced severe delayed phlebitis requiring surgical intervention. Conclusions: Accelerated E-CMF with PF is feasible achieving high DDI in a majority of pts. Non-haematological toxicity was responsible for the majority of hospital admissions which were more frequent than anticipated. Relative efficacy of this regimen requires phase III evaluation. We have also completed a second study of accelerated E-CMF where 6 cycles of intensified CMF (800/50/600mg/m2) was delivered at 14 d intervals. No significant financial relationships to disclose.