A randomised comparative trial of infusional ECisF versus conventional FEC as adjuvant chemotherapy in early breast cancer: the TRAFIC trial.
BACKGROUND
The epirubicin with cisplatin and infusional 5-fluorouracil (5-FU) (ECisF) regimen was found to be highly active in the treatment of metastatic breast cancer and as neoadjuvant therapy. The UK TRAFIC (trial of adjuvant 5-FU infusional chemotherapy) trial (CRUK/95/007) compared this schedule with 5-FU, epirubicin and cyclophosphamide (FEC60) as adjuvant therapy in patients with early breast cancer.


METHODS
In this multicentre, open-label, phase III randomised controlled trial, 349 women were randomly assigned to receive i.v. ECisF [epirubicin 60 mg/m(2), day 1, cisplatin 60 mg/m(2), day 1 and 5-FU 200 mg/m(2) by daily 24-h infusion (n = 172)] or FEC [5-FU 600 mg/m(2), day 1, epirubicin 60 mg/m(2), day 1 and cyclophosphamide 600 mg/m(2), day 1 (n = 177)]. Both treatments were delivered every 3 weeks for six cycles. The primary end point was relapse-free interval (RFI). TRAFIC is registered as an International Standard Randomised Controlled Trial (ISRCTN 83324925).


RESULTS
All randomised patients were included in the intent-to-treat population. With a median follow-up of 112 months, there was no significant difference in RFI between the treatment groups [hazard ratio 0.84 (95% confidence interval 0.60-1.19); P = 0.33]. Toxic effects were more frequent in patients allocated to ECisF.


CONCLUSIONS
While limited by size, TRAFIC has long follow-up. No evidence of a clinically worthwhile benefit for the infusional treatment compared with standard treatment was observed which would justify further investigation or widespread use.
Sirohi
B
B
Department of Medical Oncology, Max Cancer Centre, Max Healthcare, New Delhi, India (formerly at The Royal Marsden NHS Foundation Trust).
A'Hern
R
R
ICR Clinical Trials and Statistics Unit, The Institute of Cancer Research, Sutton, Surrey.
Coombes
G
G
ICR Clinical Trials and Statistics Unit, The Institute of Cancer Research, Sutton, Surrey.
Bliss
J M
JM
ICR Clinical Trials and Statistics Unit, The Institute of Cancer Research, Sutton, Surrey.
Hickish
T
T
Department of Oncology and Centre for Postgraduate Medical Research and Education, Institute of Cancer Research Clinical Trials and Statistics Unit, Royal Bournemouth Hospital, Bournemouth.
Perren
T
T
Non-Surgical Oncology, Institute of Cancer Research Clinical Trials and Statistics Unit, St James's University Hospital, Leeds.
Crawford
M
M
Medical Oncology, Airedale General Hospital, Keighley.
O'Brien
M
M
Department of Medicine, The Royal Marsden NHS Foundation Trust, London & Sutton; Mid Kent Oncology Centre, Maidstone Hospital, Sutton, Surrey.
Iveson
T
T
Oncology Department, Pembroke Suite, Salisbury District Hospital, Salisbury.
Ebbs
S
S
Breast Unit, Mayday University Hospital, Croydon.
Skene
A
A
Department of Surgery, Institute of Cancer Research Clinical Trials and Statistics Unit, Royal Bournemouth Hospital, Bournemouth.
Laing
R
R
Department of Oncology, St Luke's Cancer Centre, Guildford, UK.
Smith
I E
IE
Department of Medicine, The Royal Marsden NHS Foundation Trust, London & Sutton. Electronic address: Ian.smith@rmh.nhs.uk.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016019:Survival Analysis
D015251:Epirubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D005472:Fluorouracil