title: Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial.
abstract: BACKGROUND
  Standard adjuvant chemotherapy regimens for patients with moderate-to-high-risk early breast cancer typically contain a taxane, an anthracycline, and cyclophosphamide. We aimed to investigate whether integration of capecitabine into such a regimen enhances outcome.
  
  
  METHODS
  In this open-label trial, we randomly assigned (centrally by computer; stratified by node status, HER2 status, and centre) 1500 women with axillary node-positive or high-risk node-negative breast cancer to either three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (capecitabine group, n=753), or to three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (control group, n=747). The primary endpoint was recurrence-free survival. A planned interim analysis was done after 3 years' median follow-up. Efficacy analyses were by modified intention to treat. The study is registered with ClinicalTrials.gov, number NCT00114816.
  
  
  RESULTS
  Two patients in each group were excluded from efficacy analyses because of withdrawal of consent or distant metastases. After a median follow-up of 35 months (IQR 25.5-43.6), recurrence-free survival at 3 years was better with the capecitabine regimen than with control (93%vs 89%; hazard ratio 0.66, 95% CI 0.47-0.94; p=0.020). The capecitabine regimen was associated with more cases of grade 3 or 4 diarrhoea (46/740 [6%] vs 25/741 [3%]) and hand-foot syndrome (83/741 [11%] vs 2/741 [<1%]) and the control regimen with more occurrences of grade 3 or 4 neutropenia (368/375 [98%] vs 325/378 [86%]) and febrile neutropenia (65/741 [9%] vs 33/742 [4%]). More patients discontinued planned treatment in the capecitabine group than in the control group (178/744 [24%] vs 23/741 [3%]). Four patients in the capecitabine group and two in the control group died from potentially treatment-related causes.
  
  
  CONCLUSIONS
  The capecitabine-containing chemotherapy regimen reduced breast cancer recurrence compared with a control schedule of standard agents. Capecitabine administration was frequently discontinued because of adverse effects.
  
  
  BACKGROUND
  Roche, Sanofi-Aventis, AstraZeneca, Cancer Society of Finland.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland. heikki.joensuu@hus.fi
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.forename: Pirkko-Liisa
authors.initials: PL
authors.lastname: Kellokumpu-Lehtinen
authors.forename: Riikka
authors.initials: R
authors.lastname: Huovinen
authors.forename: Arja
authors.initials: A
authors.lastname: Jukkola-Vuorinen
authors.forename: Minna
authors.initials: M
authors.lastname: Tanner
authors.forename: Raija
authors.initials: R
authors.lastname: Asola
authors.forename: Riitta
authors.initials: R
authors.lastname: Kokko
authors.forename: Johan
authors.initials: J
authors.lastname: Ahlgren
authors.forename: Päivi
authors.initials: P
authors.lastname: Auvinen
authors.forename: Akseli
authors.initials: A
authors.lastname: Hemminki
authors.forename: Outi
authors.initials: O
authors.lastname: Paija
authors.forename: Leena
authors.initials: L
authors.lastname: Helle
authors.forename: Lauri
authors.initials: L
authors.lastname: Nuortio
authors.forename: Kenneth
authors.initials: K
authors.lastname: Villman
authors.forename: Greger
authors.initials: G
authors.lastname: Nilsson
authors.forename: Sirpa-Liisa
authors.initials: SL
authors.lastname: Lahtela
authors.forename: Kaisa
authors.initials: K
authors.lastname: Lehtiö
authors.forename: Marjo
authors.initials: M
authors.lastname: Pajunen
authors.forename: Paula
authors.initials: P
authors.lastname: Poikonen
authors.forename: Paul
authors.initials: P
authors.lastname: Nyandoto
authors.forename: Vesa
authors.initials: V
authors.lastname: Kataja
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
authors.forename: Mika
authors.initials: M
authors.lastname: Leinonen
authors.forename: Henrik
authors.initials: H
authors.lastname: Lindman
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000069287:Capecitabine; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D000069287:Capecitabine; D003520:Cyclophosphamide; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C508053:ERBB2 protein, human