Phase I Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Plus GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) Plus Dose Escalation of IL-3 (Interleukin-3) in Metastatic Breast Cancer

Inclusion Criteria

Patients with Stage IV (metastatic) breast cancer are eligible who have a
histologically-proven diagnosis. Measurable disease is not a prerequisite. Patients with
Stage III disease or Stage ll with 7 or more nodes positive are eligible.

Patients who have had prior adjuvant chemotherapy and/or hormonal therapy are eligible
providing the regimen did not include adriamycin. Patients who have had prior radiation
therapy may be eligible providing there was not extensive radiation to the cardiac area or
to greater than 20% of the bone marrow.

Patients who have received greater than 360mg/m2 of adriamycin as adjuvant therapy are
ineligible.

Patient 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/mm3 and platelet count greater than
100,000/mm3.

Liver function tests (SCOT, Alk, Phosph., and T. Bili) should be less than 1.5 time the
upper limits of normal. Serum creatinine should be less than 1.7 or creatinine clearance
should be greater than 45 ml/min unless these abnormalities are due to tumor involvement.

The patient must be able to give an informed consent, and to return to NCI for treatment
and adequate follow-up for the period the protocol requires.

No pregnant patients may be entered on this study; all patients should be informed about
the need for contraception.

Patients must be greater than or equal to 18 years of age.

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.

No patients with a history of cardiac disease must have a normal ejection fraction by MUGA
Scan and have no angina. Patients who have received prior adriamycin must have a LVEF
greater than 45%.

No history of CNS metastasis, or known seizure disorder.

No allergy to any study medication.

No pregnant or lactacting women.

No patients requiring ongoing therapy for asthma.

No patients with bleeding disorders.