title: Adjuvant Capecitabine in Combination With Docetaxel, Epirubicin, and Cyclophosphamide for Early Breast Cancer: The Randomized Clinical FinXX Trial.
abstract: OBJECTIVE
  Capecitabine is not considered a standard agent in the adjuvant treatment of early breast cancer. The results of this study suggest that addition of adjuvant capecitabine to a regimen that contains docetaxel, epirubicin, and cyclophosphamide improves survival outcomes of patients with triple-negative breast cancer (TNBC).
  
  
  OBJECTIVE
  To investigate the effect of capecitabine on long-term survival outcomes of patients with early breast cancer, particularly in subgroups defined by cancer estrogen receptor (ER) and progesterone receptor (PR) content, and HER2 content (human epidermal growth factor receptor 2).
  
  
  METHODS
  This is an exploratory analysis of the multicenter FinXX randomized clinical trial that accrued 1500 women in Finland and Sweden between January 27, 2004, and May 29, 2007. About half received 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (T+CEF), while the other half received 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (TX+CEX). Data analysis took place between January 27, 2004, and December 31, 2015.
  
  
  METHODS
  Recurrence-free survival (RFS).
  
  
  RESULTS
  Following random allocation, 747 women received T+CEF, and 753 women received TX+CEX. Five patients were excluded from the intention-to-treat population (3 had overt distant metastases at the time of randomization; 2 withdrew consent). The median age of the remaining 1495 patients was 53 years at the time of study entry; 157 (11%) had axillary node-negative disease; 1142 (76%) had ER-positive cancer; and 282 (19%) had HER2-positive cancer. The median follow-up time after random allocation was 10.3 years. There was no significant difference in RFS or overall survival between the groups (hazard ratio [HR], 0.88; 95% CI, 0.71-1.08; P = .23; and HR, 0.84, 95% CI, 0.66-1.07; P = .15; respectively). Breast cancer-specific survival tended to favor the capecitabine group (HR, 0.79; 95% CI, 0.60-1.04; P = .10). When RFS and survival of the patients were compared within the subgroups defined by cancer steroid hormone receptor status (ER and/or PR positive vs ER and PR negative) and HER2 status (positive vs negative), TX+CEX was more effective than T+CEF in the subset of patients with TNBC (HR, 0.53; 95% CI, 0.31-0.92; P = .02; and HR, 0.55, 95% CI, 0.31-0.96; P = .03; respectively).
  
  
  CONCLUSIONS
  Capecitabine administration with docetaxel, epirubicin, and cyclophosphamide did not prolong RFS or survival compared with a regimen that contained only standard agents. Patients with TNBC had favorable survival outcomes when treated with the capecitabine-containing regimen in an exploratory subgroup analysis.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00114816.
authors.affiliation: Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.affiliation: Department of Oncology, Tampere University Hospital and University of Tampere, Tampere, Finland.
authors.forename: Pirkko-Liisa
authors.initials: PL
authors.lastname: Kellokumpu-Lehtinen
authors.affiliation: Department of Oncology, Turku University Central Hospital, Turku, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Huovinen
authors.affiliation: Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland.
authors.forename: Arja
authors.initials: A
authors.lastname: Jukkola-Vuorinen
authors.affiliation: Department of Oncology, Tampere University Hospital and University of Tampere, Tampere, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Tanner
authors.affiliation: Kanta-Häme Central Hospital, Hämeenlinna, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Kokko
authors.affiliation: Gävle Hospital, Gävle, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Ahlgren
authors.affiliation: Cancer Center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Auvinen
authors.affiliation: Department of Oncology, Turku University Central Hospital, Turku, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Lahdenperä
authors.affiliation: Kotka Central Hospital, Kotka, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Kosonen
authors.affiliation: Örebro University Hospital, Örebro, Sweden.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Villman
authors.affiliation: Päijät-Häme Central Hospital, Lahti, Finland.
authors.forename: Paul
authors.initials: P
authors.lastname: Nyandoto
authors.affiliation: Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Greger
authors.initials: G
authors.lastname: Nilsson
authors.affiliation: Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Paula
authors.initials: P
authors.lastname: Poikonen-Saksela
authors.affiliation: Cancer Center, Kuopio University Hospital, Kuopio, Finland12Vaasa Central Hospital, Vaasa, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Kataja
authors.affiliation: 4Pharma, Turku, Finland.
authors.forename: Jouni
authors.initials: J
authors.lastname: Junnila
authors.affiliation: Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
authors.affiliation: Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Lindman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant / Q000379:methods / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005387:Finland / Q000453:epidemiology; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013548:Sweden / Q000453:epidemiology; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D055815:Young Adult
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D000069287:Capecitabine; D003520:Cyclophosphamide; D005472:Fluorouracil