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 may kill more tumor cells. It is not yet known whether combination chemotherapy plus epirubicin is more effective than combination chemotherapy alone for stage I or stage II breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without epirubicin in treating women who have early-stage breast cancer and who have undergone surgery to remove the tumor.

Condition	Treatment or Intervention	Phase
stage I breast cancer stage II breast cancer	Drug: cyclophosphamide  Drug: epirubicin  Drug: fluorouracil  Drug: methotrexate  Procedure: adjuvant therapy  Procedure: chemotherapy  Procedure: radiation therapy	Phase III

OBJECTIVES:

• Compare disease-free and overall survival of women with early stage breast cancer treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil with or without epirubicin.
• Compare the quality of life in a subgroup of these patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to radiotherapy timing (concurrent versus sequential), nodal status (negative versus 1-3 versus at least 4), age (50 and under versus over 50), grade, and tumor size. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive oral cyclophosphamide on days 1-14 and methotrexate IV and fluorouracil IV on days 1 and 8. Treatment repeats every 4 weeks for 6 courses.
• Arm II: Patients receive epirubicin IV on day 1 every 3 weeks for 4 courses followed by cyclophosphamide, methotrexate, and fluorouracil, as in arm I, for 4 courses. Some patients may receive radiotherapy during or after chemotherapy. Treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed in a subset of patients (N=500) before chemotherapy starts, at 3 months of treatment, at the end of chemotherapy, and at 6, 12, and 18 months after treatment.

Patients are followed annually for 10 years.

PROJECTED ACCRUAL: Approximately 2,000 patients will be accrued for this study within 4 years.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histological confirmation of invasive, early stage breast cancer
• Prior complete excision of tumor required (wide local excision or mastectomy)
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age:

• Not specified

Sex:

• Female

Menopausal status:

• Pre-, peri-, or post-menopausal

Performance status:

• Not specified

Hematopoietic:

• Adequate bone marrow function

Hepatic:

• Adequate hepatic function

Renal:

• Adequate renal function

Other:

• No prior cancer except for basal cell carcinoma or carcinoma in situ
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Concurrent hormone therapy allowed

Radiotherapy:

• No prior radiotherapy
• Concurrent radiotherapy allowed

Surgery:

• See Disease Characteristics
• No more than 6 weeks since prior surgery to the breast

United Kingdom, England
      University of Cambridge, Cambridge,  England,  CB2 2QQ,  United Kingdom; Recruiting

Study chairs or principal investigators

Helena Earl, MBBS, PhD, FRCP,  Study Chair,  University of Cambridge   

Study ID Numbers:  CDR0000066644; CRC-TU-NEAT; EU-98041
Record last reviewed:  April 2001
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003577
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-08