RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether chemotherapy is more effective with or without radiation therapy and surgery in treating breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of chemotherapy plus radiation therapy with or without surgery in treating women who have locally advanced or inflammatory breast cancer.

Condition	Treatment or Intervention	Phase
stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer inflammatory breast cancer	Drug: cyclophosphamide  Drug: docetaxel  Drug: epirubicin  Drug: filgrastim  Drug: fluorouracil  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: conventional surgery  Procedure: cytokine therapy  Procedure: neoadjuvant therapy  Procedure: radiation therapy  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES:

• Compare neoadjuvant fluorouracil, epirubicin, and cyclophosphamide vs docetaxel and epirubicin followed by radiotherapy and surgery in women with locally advanced, inflammatory, or large operable breast cancer.
• Compare the progression-free survival of patients treated with these regimens.
• Compare the distant metastasis-free survival and survival of patients treated with these regimens.
• Compare the clinical and pathological responses to these regimens in these patients.
• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to stage of disease (large T2-3 vs locally advanced or inflammatory) and participating center. Patients are randomized to 1 of 2 chemotherapy treatment arms.

• Patients receive 1 of 3 chemotherapy regimens comprising fluorouracil, epirubicin, and cyclophosphamide (FEC) (according to participating institution).
• FEC 100: Patients receive fluorouracil IV over 15 minutes, epirubicin IV over 1 hour, and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
• Canadian FEC: Patients receive oral cyclophosphamide on days 1-14 and epirubicin IV and fluorouracil IV on days 1 and 8. If oral medications are not tolerated, patients may switch to cyclophosphamide IV on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
• Tailored FEC: Patients receive fluorouracil IV over 15 minutes, epirubicin IV over 1 hour, and cyclophosphamide IV over 1-2 hours on day 1. Patients also receive filgrastim (G-CSF) subcutaneously on days 2-15 or until blood counts recover. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive docetaxel IV over 1 hour on days 1, 22, and 43 followed by epirubicin IV over 15 minutes and docetaxel IV over 1 hour on days 64, 85, and 106 in the absence of disease progression or unacceptable toxicity. Following chemotherapy, patients may undergo loco-regional therapy comprising radiotherapy with or without breast conservation surgery or mastectomy.

Patients are followed every 3 months for 1 year, every 4 months for 1.5 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 1440 patients will be accrued for this study within 4.5 years.

Ages Eligible for Study:  up to  70 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer
• Locally advanced or inflammatory disease
• T4a-d, any N, M0 OR
• Any T, N2 or N3, M0
• Large T2 or T3 breast cancer requiring tumor shrinkage prior to breast conservation surgery
• No bilateral breast cancer
• Frozen tumor sample available
• 1 incisional biopsy OR
• 2 trucut biopsies from a 14G needle
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age:

• 70 and under

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.2 mg/dL
• SGOT less than 60 IU/L

Renal:

• Creatinine less than 1.35 mg/dL

Cardiovascular:

• LVEF normal by echocardiography or MUGA

Other:

• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No serious uncontrolled medical condition
• No uncontrolled psychiatric or addictive disorders
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

Belgium
      Algemeen Ziekenhuis Sint-Augustinus, Wilrijk,  2610,  Belgium; Recruiting
      CHU Liege - Domaine Universitaire du Sart Tilman, LIEGE,  B-4000,  Belgium; Recruiting
      Institut Jules Bordet, Brussels,  1000,  Belgium; Recruiting
France
      Centre Alexis Vautrin, Vandoeuvre-les-Nancy,  54511,  France; Recruiting
      Centre Henri Becquerel, Rouen,  76038,  France; Recruiting
      Centre Hospitalier Departemental, La Roche-sur-Yon,  F-85025,  France; Recruiting
      Centre Paul Papin, Angers,  49036,  France; Recruiting
      Centre Paul Strauss, Strasbourg,  67085,  France; Recruiting
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France; Recruiting
      Centre Regional Rene Gauducheau, Nantes-Saint Herblain,  44805,  France; Recruiting
      Centre Rene Huguenin, Saint Cloud,  92211,  France; Recruiting
      Institut Bergonie, Bordeaux,  33076,  France; Recruiting
Netherlands
      Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam,  3008 AE,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
      Onze Lieve Vrouwe Gasthuis, Amsterdam,  1091 HA,  Netherlands; Recruiting
Poland
      Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw,  02-781,  Poland; Recruiting
      Medical University of Gdansk, Gdansk,  80-211,  Poland; Recruiting
Portugal
      Hospitais da Universidade de Coimbra (HUC), Coimbra,  3049,  Portugal; Recruiting
      Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, S.A., Lisbon,  1099-023 Codex,  Portugal; Recruiting
Slovenia
      Institute of Oncology - Ljubljana, LJUBLJANA,  Sl-1000,  Slovenia; Recruiting
Sweden
      Karolinska University Hospital - Huddinge, Stockholm,  S-171 76,  Sweden; Recruiting
      Lund University Hospital, Lund,  S-22185,  Sweden; Recruiting
      Malmo University Hospital, MALMO,  S-20502,  Sweden; Recruiting
      Orebro University Hospital, OREBRO,  70185,  Sweden; Recruiting
      Sahlgrenska University Hospital - Molndal at Gothenburg University, Molndal,  S-43180,  Sweden; Recruiting
      Sahlgrenska University Hospital at Gothenburg University, Gothenburg (Goteborg),  S-413 45,  Sweden; Recruiting
      Uppsala University Hospital, Uppsala,  S-75185,  Sweden; Recruiting
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland; Recruiting
      Hopital Cantonal Universitaire de Geneve, Geneva,  CH-1211,  Switzerland; Recruiting
      Inselspital, Bern, Bern,  CH-3010,  Switzerland; Recruiting
      Kantonspital Aarau, AARAU,  5001,  Switzerland; Recruiting
      Swiss Institute for Applied Cancer Research, Bern,  CH-3008,  Switzerland; Recruiting
      UniversitaetsSpital, Zurich,  CH-8091,  Switzerland; Recruiting
United Kingdom, England
      Northern Centre for Cancer Treatment at Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom; Recruiting
      Royal South Hants Hospital, Southampton,  England,  SO14 0YG,  United Kingdom; Recruiting
United Kingdom, Scotland
      Ninewells Hospital and Medical School, Dundee,  Scotland,  DD1 9SY,  United Kingdom; Recruiting
      Scottish Cancer Therapy Network, Edinburgh,  Scotland,  EH5 3SQ,  United Kingdom; Recruiting
      Western General Hospital, Edinburgh,  Scotland,  EH4 2XU,  United Kingdom; Recruiting

Study chairs or principal investigators

Herve Bonnefoi, MD,  Hopital Cantonal Universitaire de Geneve   
Jonas Bergh, MD, PhD,  Study Chair,  Karolinska University Hospital - Solna   
Barbara Muster,  Study Chair,  Swiss Institute for Applied Cancer Research   
Kirsten Murray,  Study Chair,  Scottish Cancer Therapy Network   

Study ID Numbers:  CDR0000068649; EORTC-10994; ACCOG-EORTC-10994; SAKK-EORTC-10994; SBGC-EORTC-10994; BIG-1-00; NCT00017095
Record last reviewed:  January 2005
Last Updated:  April 4, 2005
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00017095
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08