Combination Chemotherapy in Treating Women With Breast Cancer

OBJECTIVES:

• Compare the time to progression of women with primary breast cancer treated with fluorouracil, epirubicin, and cyclophosphamide vs docetaxel, epirubicin, and cyclophosphamide.
• Compare the overall survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to metastatic axillary lymph node involvement (4-9 vs 10 or more), hormone receptor status (estrogen and/or progesterone) of the primary tumor (negative vs positive), and timing of adjuvant radiotherapy (intermittently after completion of 50% of chemotherapy vs after completion of all chemotherapy). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive fluorouracil IV over 10-15 minutes and epirubicin IV over 15 minutes on days 1 and 8 and oral cyclophosphamide on days 1-14. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive epirubicin IV over 15 minutes and cyclophosphamide IV over 1 hour on days 1, 21, 42, and 63 and docetaxel IV over 1 hour on days 84, 105, 126, and 147 in the absence of disease progression or unacceptable toxicity.

Within 21 days after the completion of chemotherapy, patients undergo adjuvant radiotherapy 5 days a week for 5.5 weeks. Alternatively, patients may undergo radiotherapy intermittently after completion of 50% of chemotherapy.

Upon completion of chemotherapy, patients with positive hormone receptor status (estrogen and/or progesterone) receive oral tamoxifen daily for 5 years. Additionally, patients with positive hormone receptor status who are under age 40 receive goserelin subcutaneously every 4 weeks for 2 years.

Quality of life is assessed at baseline, prior to each course of chemotherapy, 4 weeks after completion of chemotherapy, 6 weeks after completion of radiotherapy, and then at 6 months after completion of chemotherapy.

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

PROJECTED ACCRUAL: A total of 446 patients (223 per treatment arm) will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Diagnosis of primary epithelial invasive carcinoma of the breast

• T1-4, N1-2, M0
• Must have 4 metastatic axillary lymph nodes
• Complete resection of the primary tumor within the past 5 weeks

• Free of invasive carcinoma with at least 10 lymph nodes removed
• No inflammatory breast cancer
• No distant metastases by chest x-ray, liver ultrasound, and whole body bone scan
• Hormone receptor status:

• Estrogen and/or progesterone receptor status known

PATIENT CHARACTERISTICS:

Age

• 18 to 70

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• At least 32 weeks

Hematopoietic

• WBC at least 3,000/mm3
• Platelet count at least 100,000

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT/SGPT no greater than 1.5 times ULN
• Alkaline phosphatase no greater than 1.5 times ULN
• Albumin no greater than 1.5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No cardiomyopathy with impaired ventricular function
• No New York Heart Association class III or IV heart disease
• No cardiac arrhythmias influencing LVEF and requiring medication
• No myocardial infarction within the past 6 months
• No angina pectoris within the past 6 months
• No uncontrolled arterial hypertension

Other

• No other primary malignancy except carcinoma in situ of the cervix or adequately treated basal cell skin cancer
• No known hypersensitivity to docetaxel, epirubicin, fluorouracil, cyclophosphamide, or other study medication
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior cytotoxic or other antineoplastic therapy
• No other concurrent cytotoxic or other antineoplastic therapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 3 weeks since prior investigational agents