RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill any tumor cells remaining after surgery. It is not yet known which combination chemotherapy regimen is more effective in treating resected stage I or stage II breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens in treating women who have resected stage I or stage II breast cancer.

Condition	Treatment or Intervention	Phase
stage I breast cancer stage II breast cancer	Drug: cyclophosphamide  Drug: docetaxel  Drug: epirubicin  Drug: fluorouracil  Drug: methotrexate  Drug: tamoxifen  Procedure: adjuvant therapy  Procedure: antiestrogen therapy  Procedure: chemotherapy  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: radiation therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the disease-free and overall survival of women with completely resected stage I or II breast cancer adjuvantly treated with fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil (EPI-CMF) versus FEC followed by sequential docetaxel.
• Compare the acute toxicity of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, estrogen receptor status (positive vs negative), and nodal status. Within 8 weeks after definitive surgery, patients are randomized to 1 of 2 treatment arms.

• Patients are assigned to 1 of 2 standard adjuvant chemotherapy regimens.
• Regimen A: Patients receive fluorouracil, epirubicin, and cyclophosphamide (FEC) IV on day 1. Treatment repeats every 3 weeks for 8 courses.
• Regimen B: Patients receive epirubicin IV on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive cyclophosphamide orally on days 1-14 or IV on days 1 and 8 and methotrexate IV and fluorouracil IV on days 1 and 8 (CMF). Treatment with CMF repeats every 4 weeks for 4 courses.
• Arm II: Patients receive 4 courses of adjuvant chemotherapy with FEC as in arm I, regimen A. Patients then receive sequential docetaxel IV over 1 hour once every 3 weeks for 4 courses. Beginning within 4 weeks after completion of adjuvant chemotherapy, patients who are not concurrently enrolled in the Standardization of Breast Radiotherapy (START) trial receive localized radiotherapy once daily, 5 days a week, for 3-5 weeks, according to local practice.

Beginning within 4 weeks after completion of adjuvant chemotherapy, patients who are estrogen receptor and/or progesterone receptor positive receive oral tamoxifen once daily for at least 5 years.

Quality of life is assessed at baseline, before course 5, at 3-4 weeks after course 8, and then at 9, 12, 18, and 24 months after initiation of adjuvant chemotherapy.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 3,340 patients (1,670 per treatment arm) will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed completely resected, invasive breast cancer for which adjuvant chemotherapy is indicated
• No clinical or radiological evidence of locoregional or metastatic disease
• No locally advanced tumors at diagnosis, indicated by any of the following:
• Fixed tumors
• Peau d'orange skin changes
• Skin ulceration
• Inflammatory changes (T4 or T3b, N2 disease)
• No male breast cancer
• No prior invasive breast cancer or bilateral breast cancer
• Prior ductal carcinoma in situ or lobular carcinoma in situ is allowed
• Must begin study chemotherapy within 8 weeks after definitive surgery
• Hormone receptor status:
• Estrogen receptor and progesterone receptor status known

PATIENT CHARACTERISTICS: Age:

• Over 18

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• WHO 0-1

Life expectancy:

• At least 2 years

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin normal
• AST no greater than 1.5 times normal
• Alkaline phosphatase no greater than 1.5 times normal

Renal:

• Creatinine no greater than 1.5 times normal

Cardiovascular:

• No myocardial infarction within the past 6 months
• No congestive heart failure

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other invasive malignancy within the past 10 years except surgically cured nonmelanoma skin cancer or carcinoma in situ of the cervix
• No other serious medical illness that would limit life expectancy
• No psychiatric condition that would preclude informed consent
• No active uncontrolled bacterial, viral, or fungal infection

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• See Disease Characteristics
• No prior cytotoxic chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy (e.g., tamoxifen) during study chemotherapy
• No concurrent hormone replacement therapy

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

Other:

• At least 4 weeks since any prior unlicensed drugs
• No other concurrent experimental drugs

Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
United Kingdom, England
      Alexandra Healthcare NHS, Redditch, Worcestershire,  England,  B98 7UB,  United Kingdom; Recruiting
      Blackpool Victoria Hospital, Blackpool,  England,  FY3 8NR,  United Kingdom; Recruiting
      Bradford Hospitals NHS Trust, Bradford,  England,  BD9 6RJ,  United Kingdom; Recruiting
      Bristol Haematology and Oncology Centre, Bristol,  England,  BS2 8ED,  United Kingdom; Recruiting
      Broomfield Hospital, Chelmsford, Essex,  England,  CM1 5ET,  United Kingdom; Recruiting
      Cancer Research Centre at Weston Park Hospital, Sheffield,  England,  S1O 2SJ,  United Kingdom; Recruiting
      Charing Cross Hospital, London,  England,  W6 8RF,  United Kingdom; Recruiting
      Cheltenham General Hospital, Cheltenham,  England,  GL53 7AN,  United Kingdom; Recruiting
      Christie Hospital N.H.S. Trust, Manchester,  England,  M20 4BX,  United Kingdom; Recruiting
      City Hospital - Birmingham, Birmingham,  England,  B18 7QH,  United Kingdom; Recruiting
      Clatterbridge Centre for Oncology NHS Trust, MERSEYSIDE,  England,  CH63 4JY,  United Kingdom; Recruiting
      Cookridge Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS16 6QB,  United Kingdom; Recruiting
      Derbyshire Royal Infirmary, Derby,  England,  DE1 2QY,  United Kingdom; Recruiting
      Diana Princess of Wales Hospital, Grimsby,  England,  DN33 2BA,  United Kingdom; Recruiting
      Essex County Hospital, Colchester,  England,  C03 3NB,  United Kingdom; Recruiting
      Guy's Hospital, London,  England,  SE1 9RT,  United Kingdom; Recruiting
      Huddersfield Royal Infirmary, Huddersfield, West Yorks,  England,  HD3 3EA,  United Kingdom; Recruiting
      Ipswich Hospital NHS Trust, Ipswich,  England,  IP4 5PD,  United Kingdom; Recruiting
      Leicester Royal Infirmary, Leicester,  England,  LE1 5WW,  United Kingdom; Recruiting
      Maidstone Hospital, Maidstone,  England,  ME16 9QQ,  United Kingdom; Recruiting
      Meyerstein Institute of Oncology at University College of London Hospitals, London,  England,  WIT 3AA,  United Kingdom; Recruiting
      Mount Vernon Hospital, Northwood,  England,  HA6 2RN,  United Kingdom; Recruiting
      New Cross Hospital, Wolverhampton,  England,  WV10 0QP,  United Kingdom; Recruiting
      North Devon District Hospital, Barnstaple,  England,  EX31 4JB,  United Kingdom; Recruiting
      North Staffs Royal Infirmary, Stoke on Trent,  England,  ST4 7LN,  United Kingdom; Recruiting
      Northampton General Hospital NHS Trust, Northampton,  England,  NN6 8BJ,  United Kingdom; Recruiting
      Northern Centre for Cancer Treatment at Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom; Recruiting
      Oldchurch Hospital, Romford,  England,  RM7 OBE,  United Kingdom; Recruiting
      Oxford Radcliffe Hospital, Oxford,  England,  0X3 9DU,  United Kingdom; Recruiting
      Peterborough Hospitals Trust, Peterborough,  England,  PE3 6DA,  United Kingdom; Recruiting
      Pilgrim Hospital, Boston,  England,  PE21 9QT,  United Kingdom; Recruiting
      Portsmouth Oncology Centre at Saint Mary's Hospital, Portsmouth Hants,  England,  PO3 6AD,  United Kingdom; Recruiting
      Princess Royal Hospital, Hull,  England,  HU8 9HE,  United Kingdom; Recruiting
      Queen Elizabeth Hospital at University of Birmingham, Birmingham,  England,  B15 2TH,  United Kingdom; Recruiting
      Queen Elizabeth Hospital, King's Lynn,  England,  PE30 4ET,  United Kingdom; Recruiting
      Royal Berkshire Hospital, Reading,  England,  RG1 5AN,  United Kingdom; Recruiting
      Royal Devon and Exeter Hospital, Exeter,  England,  EX2 5DW,  United Kingdom; Recruiting
      Royal Free and University College Medical School, Hampstead, London,  England,  NW3 2QG,  United Kingdom; Recruiting
      Royal Marsden NHS Foundation Trust - Surrey, Sutton,  England,  SM2 5PT,  United Kingdom; Recruiting
      Royal Preston Hospital, Preston,  England,  PR2 9HT,  United Kingdom; Recruiting
      Royal Shrewsbury Hospital, Shrewsbury,  England,  SY3 8XQ,  United Kingdom; Recruiting
      Royal South Hants Hospital, Southampton,  England,  SO14 0YG,  United Kingdom; Recruiting
      Royal Sussex County Hospital, Brighton,  England,  BN2 5BF,  United Kingdom; Recruiting
      Royal United Hospital, Bath,  England,  BA1 3NG,  United Kingdom; Recruiting
      Saint Bartholomew's Hospital, London,  England,  EC1A 7BE,  United Kingdom; Recruiting
      Salisbury District Hospital, Salisbury,  England,  SP2 8BJ,  United Kingdom; Recruiting
      Scunthorpe General Hospital, Scunthorpe,  England,  DN15 7BH,  United Kingdom; Recruiting
      Southend NHS Trust Hospital, Westcliff-On-Sea,  England,  SS0 0RY,  United Kingdom; Recruiting
      St. Georges Hospital Medical School, London,  England,  SW17 ORE,  United Kingdom; Recruiting
      St. James's University Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS9 7TF,  United Kingdom; Recruiting
      St. Luke's Cancer Centre at Royal Surrey County Hospital, Guildford,  England,  GU2 5XX,  United Kingdom; Recruiting
      Taunton and Somerset Hospital, Taunton Somerset,  England,  TA1 5DA,  United Kingdom; Recruiting
      Torbay Hospital, Torquay Devon,  England,  TQ2 7AA,  United Kingdom; Recruiting
      University of Cambridge, Cambridge,  England,  CB2 2QQ,  United Kingdom; Recruiting
      Walsgrave Hospital, Coventry,  England,  CV2 2DX,  United Kingdom; Recruiting
      West Suffolk Hospital, Bury St. Edmunds,  England,  IP33 2QZ,  United Kingdom; Recruiting
United Kingdom, Northern Ireland
      Belfast City Hospital Trust Incorporating Belvoir Park Hospital, Belfast,  Northern Ireland,  BT8 8JR,  United Kingdom; Recruiting
United Kingdom, Scotland
      Aberdeen Royal Infirmary, Aberdeen,  Scotland,  AB25 2ZN,  United Kingdom; Recruiting
      Beatson Oncology Centre, Glasgow,  Scotland,  G11 6NT,  United Kingdom; Recruiting
      Hairmyres Hospital, East Kilbride,  Scotland,  G75 8RG,  United Kingdom; Recruiting
      Ninewells Hospital and Medical School, Dundee,  Scotland,  DD1 9SY,  United Kingdom; Recruiting
      Raigmore Hospital, Inverness,  Scotland,  1V2 3UJ,  United Kingdom; Recruiting
      Royal Infirmary - Castle, Glasgow,  Scotland,  G4 0SF,  United Kingdom; Recruiting
      Western General Hospital, Edinburgh,  Scotland,  EH4 2XU,  United Kingdom; Recruiting
United Kingdom, Wales
      Bronglais General Hospital - Ceredigion and Mid Wales NHS trust, Aberystwyth,  Wales,  SY23 1ER,  United Kingdom; Recruiting
      Glan Clywd District General Hospital, Rhyl, Denbighshire,  Wales,  LL 18 5UJ,  United Kingdom; Recruiting
      Singleton Hospital, Swansea,  Wales,  SA 2 8QA,  United Kingdom; Recruiting
      Velindre Cancer Center at Velinde Hospital, Cardiff,  Wales,  CF14 2TL,  United Kingdom; Recruiting

Study chairs or principal investigators

Paul Ellis, MD,  Study Chair,  Guy's Hospital   

Study ID Numbers:  CDR0000069311; ICR-TACT; EU-20109; NCT00033683
Record last reviewed:  April 2002
Last Updated:  April 4, 2005
Record first received:  April 9, 2002
ClinicalTrials.gov Identifier:  NCT00033683
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08