A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer

Patients with Stage IV (metastatic) breast cancer who have a histologically-proven diagnosis. Measurable, evaluable Stage III patients, Stage II patients with 4 or more nodes positive, and Stage IV NED (no evidence of disease) patients. Patients who have had prior radiation therapy providing there was not more than 20% of the bone marrow has been irradiated. Patients who have received less than or equal to 360mg/m2 of Adriamycin as adjuvant therapy. Patients must be previously untreated with chemotherapy for metastatic disease. There must be no history of previous malignancy except for cured non-melanoma skin cancer (basal or squamous cell carcinoma), cervical cancer in situ, or a past malignancy that has been inactive for over 5 years. Performance status (Karnofsky scale) must be greater than 70; ECOG 0-2. Absolute granulocyte count greater than 1500 microliters and platelet count greater than 100,000/mm3. Liver function tests (SGOT, and total bilirubin) should be less than 2X the upper limits of normal unless there is evidence of hepatic involvement with tumor. Serum creatinine should be less than 1.7 or creatinine clearance should be greater than 45 ml/min. Patients must be greater than or equal to 18 years of age. The patient must be able to give informed consent, and to return to NCI for treatment and adequate follow-up for the period the protocol requires. No patients who are poor medical or psychiatric risks because of nonmalignant systemic disease which would preclude them from being subjected to any treatments in this protocol. Patients should not currently require therapy for cardiac arrhythmias, congestive heart failure, or coronary artery disease. Patients who have received prior Adriamycin or have any history of cardiac disease must have a LVEF greater than 45 percent by MUGA. No history of CNS metastasis, or know seizure disorder. No allergy to any study medication. No pregnant or lactating women. No patients requiring ongoing therapy for asthma. No patients with bleeding disorders for study entry as are patients requiring chronic anticoagulation. No patients with active infection or are known to be HIV positive.