PHASE-I TRIAL OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR DERIVED FROM YEAST IN PATIENTS WITH BREAST-CANCER RECEIVING CYCLOPHOSPHAMIDE, DOXORUBICIN, AND FLUOROURACIL

Purpose: To establish the optimum biologic dose and maximal-tolerated dose (MTD) of once-daily, subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor derived from yeast (RhuGM-CSF) in patients with breast cancer. Patients and Methods: Seventeen patients with either newly diagnosed breast cancer with more than four involved axillary nodes (five patients) or metastatic breast cancer (12 patients) were treated with cyclophosphamide 1 g/m2, doxorubicin 50 mg/m2, and fluorouracil 500 mg/m2 (CAF) intravenously (IV) once every 3 weeks. RhuGM-CSF was administered subcutaneously once daily for 14 days after the second and third CAF cycles, at one of three dose levels. Results: The 125-μg/m2/d RhuGM-CSF dose level shortened the duration of neutropenia in only one of three patients. The 250- μg/m2/d level was effective in shortening the duration of the neutropenic nadir (< .5 x 109/dL) by 2 or more days in five of six patients. The 500- μg/m2/d level caused severe toxicity (chest pain, two patients; deep vein thrombosis, one patient) in three of eight patients. Conclusion: RhuGM-CSF administered once daily at the 250-μg/m2/d level is well tolerated and effective in shortening the duration of the neutrophil nadir by 2 or more days after CAF therapy.