RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs in different combinations may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of cyclophosphamide, methotrexate, and fluorouracil with mitoxantrone in treating older patients with recurrent or metastatic breast cancer.

OBJECTIVES: I. Determine the response rate and duration of response of elderly patients with advanced breast cancer treated with first-line chemotherapy with mitigated "classical" CMF (cyclophosphamide/methotrexate/fluorouracil) vs. mitoxantrone (DHAD).

II. Define the morbidity of CMF and DHAD in elderly patients.

III. Determine quality of life in these patients.

PROTOCOL OUTLINE: This is a randomized study. Patients are stratified by participating institution.

The first group receives oral cyclophosphamide on days 1 through 14 and intravenous methotrexate and fluorouracil on days 1 and 8. Courses repeat every 4 weeks for a maximum of 6 courses.

The second group receives intravenous mitoxantrone every 3 weeks for a maximum of 8 courses.

Concomitant therapy with hepatotoxic or nephrotoxic drugs (e.g., NSAIDs) or corticosteroids (even as antiemetics) is not permitted in either group. Radiotherapy is allowed provided no more than 50% of the bone marrow is irradiated and at least 1 indicator lesion is unirradiated.

Patients who complete therapy are followed every 3 months until disease progression.

PROJECTED ACCRUAL: 60 patients will be accrued over approximately 1 year. If extreme differences between arms exist after entry of 30 patients, accrual may be stopped early.

Ages Eligible for Study:  70 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven, progressive, recurrent or metastatic breast cancer in patients over 70 years of age
• Measurable or evaluable disease required, including: Lesions of the mediastinum, retroperitoneum, or liver at least 3 cm in diameter on CT scan or ultrasound
• The following are not considered measurable or evaluable: Lymphedema; Hilar enlargement; Pleural effusion; Ascites; Bone marrow infiltration; Osteoblastic skeletal lesion
• No CNS metastases
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy for advanced disease; At least 1 year since prior adjuvant chemotherapy
• Endocrine therapy: At least 4 weeks since prior estrogens, androgens, and progestins; Tamoxifen or aminoglutethimide allowed with no waiting period if disease progresses; Recovery from prior hormonal therapy for metastatic disease required
• Radiotherapy: Prior radiotherapy allowed provided: Evaluable disease exists outside of treatment field; No greater than 50% of bone marrow was irradiated
• Surgery: Not specified

--Patient Characteristics--

• Age: Over 70
• Sex: Not specified
• Menopausal status: Postmenopausal
• Performance status: WHO 0-2
• Hematopoietic: WBC at least 3,000; Platelets at least 100,000
• Hepatic: Bilirubin less than 1.4 mg/dL (25 micromoles/L)
• Renal: Creatinine clearance (calculated) greater than 50 mL/min in patients weighing at least 45 kg and measured creatinine clearance at least 50 mL/min in patients weighing less than 45 kg
• Cardiovascular: No congestive heart failure; No myocardial infarction within 6 months; No severe arrhythmia; No complete bundle branch block
• Other: No active uncontrolled infection; No mental disorders that may preclude patient follow-up; No second malignancy except: Adequately treated basal cell carcinoma of the skin; Adequately treated in situ carcinoma of the cervix