title: Cyclophosphamide, epirubicin, and Fluorouracil versus dose-dense epirubicin and cyclophosphamide followed by Paclitaxel versus Doxorubicin and cyclophosphamide followed by Paclitaxel in node-positive or high-risk node-negative breast cancer.
abstract: PURPOSE Cyclophosphamide, epirubicin, and fluorouracil (CEF) and doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) are commonly used adjuvant regimens in women with early breast cancer. In a previous trial in women with locally advanced breast cancer, 3 months of high-dose epirubicin and cyclophosphamide (EC) administered every 2 weeks (dose-dense) was equivalent to 6 months of CEF. We hypothesized that 3 months of paclitaxel after dose-dense EC (EC/T) would be superior to CEF or AC/T. METHODS After lumpectomy or mastectomy, women 60 years of age or younger with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive CEF, EC/T, or AC/T for 6 months. This article reports the interim analysis for recurrence-free survival (RFS), which was planned after 227 recurrences. Results A total of 2,104 patients were enrolled. The median follow-up is 30.4 months. Hazard ratios for recurrence are as follows: AC/T versus CEF, 1.49 (95% CI, 1.12 to 1.99), P = .005; AC/T versus EC/T, 1.68 (95% CI, 1.25 to 2.27), P = .0006; and EC/T versus CEF, 0.89 (95% CI, 0.64 to 1.22), P = .46. Three-year RFS rates for CEF, EC/T, and AC/T are 90.1%, 89.5%, and 85.0%, respectively. There was more febrile neutropenia with CEF (22.3%) and EC/T (16.4%) compared with AC/T (4.8%), but more neuropathy with the last two regimens. CONCLUSION Three-weekly AC/T is significantly inferior to CEF or EC/T in terms of RFS. It is too early to detect any difference between CEF and dose-dense EC/T.
authors.affiliation: Atlantic Health Sciences Corporation, Saint John, New Brunswick, NJ, USA.
authors.forename: Margot
authors.initials: M
authors.lastname: Burnell
authors.forename: Mark N
authors.initials: MN
authors.lastname: Levine
authors.forename: Judith-Anne W
authors.initials: JA
authors.lastname: Chapman
authors.forename: Vivien
authors.initials: V
authors.lastname: Bramwell
authors.forename: Karen
authors.initials: K
authors.lastname: Gelmon
authors.forename: Barbara
authors.initials: B
authors.lastname: Walley
authors.forename: Ted
authors.initials: T
authors.lastname: Vandenberg
authors.forename: Haji
authors.initials: H
authors.lastname: Chalchal
authors.forename: Kathy S
authors.initials: KS
authors.lastname: Albain
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Hope
authors.initials: H
authors.lastname: Rugo
authors.forename: Kathleen
authors.initials: K
authors.lastname: Pritchard
authors.forename: Patti
authors.initials: P
authors.lastname: O'Brien
authors.forename: Lois E
authors.initials: LE
authors.lastname: Shepherd
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage
chemical_list: D015251:Epirubicin; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil