title: Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial.
abstract: BACKGROUND
  Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration.
  
  
  METHODS
  In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2), cyclophosphamide 600 mg/m(2) at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m(2) at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m(2) at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493.
  
  
  RESULTS
  All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0.95, 95% CI 0.85-1.08; p=0.44). 75.6% (95% CI 73.7-77.5) of patients in the experimental group and 74.3% (72.3-76.2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0.0001); the most frequent events were neutropenia (937 events vs 797 events), leucopenia (507 vs 362), and lethargy (456 vs 272).
  
  
  CONCLUSIONS
  This study did not show any overall gain from the addition of docetaxel to standard anthracycline chemotherapy. Exploration of predictive biomarker-defined subgroups might have the potential to better target the use of taxane-based therapy.
  
  
  BACKGROUND
  Cancer Research UK (CRUK 01/001), Sanofi-Aventis, Pfizer, and Roche.
authors.affiliation: Guy's and St Thomas' NHS Trust, London, UK. paul.ellis@gstt.nhs.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Ellis
authors.forename: Peter
authors.initials: P
authors.lastname: Barrett-Lee
authors.forename: Lindsay
authors.initials: L
authors.lastname: Johnson
authors.forename: David
authors.initials: D
authors.lastname: Cameron
authors.forename: Andrew
authors.initials: A
authors.lastname: Wardley
authors.forename: Susan
authors.initials: S
authors.lastname: O'Reilly
authors.forename: Mark
authors.initials: M
authors.lastname: Verrill
authors.forename: Ian
authors.initials: I
authors.lastname: Smith
authors.forename: John
authors.initials: J
authors.lastname: Yarnold
authors.forename: Robert
authors.initials: R
authors.lastname: Coleman
authors.forename: Helena
authors.initials: H
authors.lastname: Earl
authors.forename: Peter
authors.initials: P
authors.lastname: Canney
authors.forename: Chris
authors.initials: C
authors.lastname: Twelves
authors.forename: Christopher
authors.initials: C
authors.lastname: Poole
authors.forename: David
authors.initials: D
authors.lastname: Bloomfield
authors.forename: Penelope
authors.initials: P
authors.lastname: Hopwood
authors.forename: Stephen
authors.initials: S
authors.lastname: Johnston
authors.forename: Mitchell
authors.initials: M
authors.lastname: Dowsett
authors.forename: John M S
authors.initials: JM
authors.lastname: Bartlett
authors.forename: Ian
authors.initials: I
authors.lastname: Ellis
authors.forename: Clare
authors.initials: C
authors.lastname: Peckitt
authors.forename: Emma
authors.initials: E
authors.lastname: Hall
authors.forename: Judith M
authors.initials: JM
authors.lastname: Bliss
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001530:Belgium / Q000453:epidemiology; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D042241:Early Diagnosis; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D053609:Lethargy / Q000139:chemically induced; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D011960:Receptors, Estrogen; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil