1. ¹Oncology Centre, Addenbrookes Hospital, University of Cambridge, Cambridge CB2 0QQ, UK
2. ²Warwick Medical School Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK
3. ³Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham B15 2TT, UK
4. ⁴Department of Clinical and Health Psychology, St James's University Hospital, Leeds LS9 7TF, UK
5. ⁵St Chads Pharmacy Department, City Hospital, Birmingham B18 7QH, UK
6. ⁶Arden Cancer Centre, University Hospital, Coventry CV2 2DX, UK
7. ⁷Department of Oncology, Royal Shrewsbury Hospital, Shrewsbury SY3 8XQ, UK
8. ⁸Cancer Centre, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
9. ⁹Staffordshire Oncology Centre, University Hospital of North Staffordshire, North Staffordshire ST4 7LN, UK
10. ¹⁰Peterborough District Hospital, Cambridgeshire PE3 6DA, UK
11. ¹¹Clatterbridge Oncology Centre, Merseyside CH63 4JY, UK

Correspondence: Dr HM Earl, Department of Oncology, University of Cambridge, Addenbrookes Hospital (Box 193–R4), Cambridge CB2 0QQ, UK. E-mail: hme22@cam.ac.uk

Received 22 July 2008; Revised 21 August 2008; Accepted 22 August 2008; Published online 16 September 2008.

Abstract

The NEAT trial reported considerable benefit for ECMF (epirubicin followed by cyclophosphamide, methotrexate and 5-fluorouracil) of 28% for relapse-free survival (RFS) and 30% for overall survival (OS), when compared with classical CMF in early breast cancer. To assess tolerability, toxicity, dose intensity and quality of life (QoL) analyses were undertaken. All 2021 eligible patients had common toxicity criteria (CTC), delivered chemotherapy and supportive treatments details and long-term morbidities recorded. The QoL substudy used multiple validated measures. ECMF produced low CTC scores, although higher than CMF for nausea, vomiting, alopecia, constipation, stomatitis (P<0.001), infection (P=0.001) and fatigue (P=0.03). Supportive treatments required, however, were similar across randomised treatments. On-treatment deaths were more common with CMF (13) than ECMF(5). Optimal course-delivered dose intensity (CDDI 85%) was received more often by ECMF patients (83 vs 76%: P=0.0002), and was associated with better RFS (P=0.0006). QoL over 2 years was equivalent across treatments, despite minimally worse side effects for ECMF during treatment. ECMF benefit spanned all levels of toxicity, CDDI and QoL. There are no reported acute myeloid leukaemias or cardiac dysfunctions. ECMF is tolerable, deliverable, and significantly more effective than CMF, with no serious long-term toxicity or QoL detriment.