Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial.
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.
Ellis
Paul
P
Guy's and St Thomas' NHS Trust, London, UK. paul.ellis@gstt.nhs.uk
Barrett-Lee
Peter
P
Johnson
Lindsay
L
Cameron
David
D
Wardley
Andrew
A
O'Reilly
Susan
S
Verrill
Mark
M
Smith
Ian
I
Yarnold
John
J
Coleman
Robert
R
Earl
Helena
H
Canney
Peter
P
Twelves
Chris
C
Poole
Christopher
C
Bloomfield
David
D
Hopwood
Penelope
P
Johnston
Stephen
S
Dowsett
Mitchell
M
Bartlett
John M S
JM
Ellis
Ian
I
Peckitt
Clare
C
Hall
Emma
E
Bliss
Judith M
JM
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
D000970:Antineoplastic Agents; D011960:Receptors, Estrogen; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil