title: NEAT: National Epirubicin Adjuvant Trial--toxicity, delivered dose intensity and quality of life.
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 > or =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.
authors.affiliation: Oncology Centre, Addenbrookes Hospital, University of Cambridge, Cambridge CB2 0QQ, UK. hme22@cam.ac.uk
authors.forename: H M
authors.initials: HM
authors.lastname: Earl
authors.forename: L
authors.initials: L
authors.lastname: Hiller
authors.forename: J A
authors.initials: JA
authors.lastname: Dunn
authors.forename: S
authors.initials: S
authors.lastname: Bathers
authors.forename: P
authors.initials: P
authors.lastname: Harvey
authors.forename: A
authors.initials: A
authors.lastname: Stanley
authors.forename: R J
authors.initials: RJ
authors.lastname: Grieve
authors.forename: R K
authors.initials: RK
authors.lastname: Agrawal
authors.forename: I N
authors.initials: IN
authors.lastname: Fernando
authors.forename: A M
authors.initials: AM
authors.lastname: Brunt
authors.forename: K
authors.initials: K
authors.lastname: McAdam
authors.forename: S
authors.initials: S
authors.lastname: O'Reilly
authors.forename: D W
authors.initials: DW
authors.lastname: Rea
authors.forename: D
authors.initials: D
authors.lastname: Spooner
authors.forename: C J
authors.initials: CJ
authors.lastname: Poole
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008727:Methotrexate / Q000008:administration & dosage; D011788:Quality of Life
chemical_list: D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate
references.citation: JAMA. 1995 Feb 15;273(7):542-7
references.pmid: 7837388
references.citation: J Clin Oncol. 1984 Nov;2(11):1281-8
references.pmid: 6387060
references.citation: N Engl J Med. 2006 Nov 2;355(18):1851-62
references.pmid: 17079759
references.citation: Br J Cancer. 1977 Jan;35(1):1-39
references.pmid: 831755
references.citation: N Engl J Med. 1995 Apr 6;332(14):901-6
references.pmid: 7877646
references.citation: Stat Med. 2000 Oct 15;19(19):2657-74
references.pmid: 10986540
references.citation: J Clin Oncol. 1996 Oct;14(10):2756-68
references.pmid: 8874337
references.citation: Lancet. 1992 Jan 11;339(8785):71-85
references.pmid: 1345869
references.citation: Lancet. 1998 Sep 19;352(9132):930-42
references.pmid: 9752815
references.citation: Biometrics. 1984 Dec;40(4):1079-87
references.pmid: 6534410
references.citation: J Natl Cancer Inst. 1993 Mar 3;85(5):365-76
references.pmid: 8433390