DOSING REGIMEN OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR TO SUPPORT DOSE-INTENSIVE CHEMOTHERAPY

Purpose: This trial evaluated the optimum dosing regimen for recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) to support a dose-intensive chemotherapy regimen given without progenitor cell replacement. Patients and Methods: Fifty-one patients with refractory malignancy received cyclophosphamide 2,500 mg/m2 on days 1 and 2, etoposide 500 mg/m2 on days 1, 2, and 3, and cisplatin 50 mg/m2 on days 1, 2, and 3. Patients were hospitalized from cycle days 1 to 4 for chemotherapy and readmitted for cytopenic temperatures above 38.5°C. Cycles were repeated every 35 days in patients who responded to a total of three cycles. GM-CSF was given at doses of 250 to 1,000 μg/m2 by continuous intravenous infusion (CIV) or subcutaneously starting on cycle days 3 to 6. Two nonrandomized control groups are used. Results: The optimum regimen of GM-CSF for shortening the duration of leukopenia (WBC count < 300/μL) was 500 μg/m2 given CIV. Duration of leukopenia was 5.9 days compared with 13.2 and 10.2 days in the controls (P < .05). The optimum regimens for shortening duration of hospitalization, however, were 500 and 750 μg/m2/d given as divided (twice daily) subcutaneous injections. Durations of hospitalization were 9.6 and 9.8 days compared with 15.7 and 22.2 days in the controls (P < .08). At the higher GM-CSF dose, only 36% of patients required readmission for cytopenic fever. Toxicities of GM-CSF at clinically useful doses were minimal. Twelve patients had complete response (24%) and 22 partial response (43%). Conclusions: This dose-intensive regimen can be given safely without progenitor replacement. rhu GM-CSF decreases the duration of severe leukopenia and decreases the need for hospitalization and antibiotic therapy.