RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumors cells. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which regimen of chemotherapy plus radiation therapy is more effective for early-stage breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of adjuvant chemotherapy plus radiation therapy in treating women who have early-stage breast cancer.

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

OBJECTIVES:

• Compare the effects of synchronous vs sequential adjuvant chemotherapy and radiotherapy on local recurrence, disease-free and overall survival, and treatment delay in women with early-stage breast cancer.
• Compare the safety of these regimens, in terms of dose intensity and toxicity, in this patient population.
• Compare the quality of life and cosmetic outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinical oncologist, axillary clearance (yes vs no), radiotherapy boost intent (boost vs no boost), and chemotherapy intent (cyclophosphamide, methotrexate, and fluorouracil [5-FU] vs anthracycline-containing regimen). Patients are randomized to one of two treatment arms.

Patients receive any chemotherapy regimen that includes cyclophosphamide, methotrexate, and 5-FU. Some regimens may also include epirubicin, doxorubicin, mitoxantrone, and/or mitomycin. Chemotherapy repeats every 3 weeks for 4-8 courses.

• Arm I (synchronous chemoradiotherapy): Patients receiving synchronous therapy receive any of the above chemotherapy regimens plus daily radiotherapy between courses 2 and 3 OR courses 5 and 6 of chemotherapy. Radiotherapy is administered for 3-5 weeks.
• Arm II (sequential chemoradiotherapy): Patients receiving sequential therapy receive any of the above chemotherapy regimens followed by daily radiotherapy beginning after completion of all chemotherapy (after course 6 or 8). Radiotherapy is administered for 3-5 weeks. Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed before chemotherapy, 2-3 weeks after the completion of all treatment, and then at 1, 2, and 5 years.

Patients are followed annually for 10 years.

PROJECTED ACCRUAL: A total of 2,250 patients (1,125 per treatment arm) will be accrued for this study.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer
• Early-stage disease
• No metastatic disease
• Complete surgical excision of tumor
• Planned use of adjuvant chemotherapy and radiotherapy
• If participating in the cosmetic outcome evaluation portion of the study, must have unilateral disease
• Hormone receptor status
• Not specified

PATIENT CHARACTERISTICS: Age:

• Not specified

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Bone marrow function adequate

Hepatic:

• Hepatic function adequate

Renal:

• Renal function adequate

Cardiovascular:

• Cardiac function adequate

Other:

• No other prior malignancy except basal cell or squamous cell skin cancer or carcinoma in situ
• No other medical or social condition that would preclude study compliance
• Fit to receive both adjuvant chemotherapy and radiotherapy (administered either synchronously or sequentially)
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No prior chemotherapy
• No concurrent epirubicin and doxorubicin as a study combination chemotherapy regimen

Endocrine therapy:

• Prior or concurrent hormonal therapy allowed
• No concurrent tamoxifen if treated with methotrexate, mitomycin, and mitoxantrone as a study combination chemotherapy regimen

Radiotherapy:

• See Disease Characteristics
• No concurrent internal mammary chain irradiation
• No concurrent orthovoltage irradiation to the whole breast

Surgery:

• See Disease Characteristics
• Recovered from prior surgery

Other:

• Concurrent participation in another clinical trial allowed

United Kingdom, England
      Queen Elizabeth Hospital at University of Birmingham, Birmingham,  England,  B15 2TH,  United Kingdom; Recruiting

Study chairs or principal investigators

Indy Fernando, MD,  Study Chair,  Queen Elizabeth Hospital at University of Birmingham   

Study ID Numbers:  CDR0000067062; CRC-TU-BR3015; EU-99005
Record last reviewed:  June 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003893
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-05