Dosing regimen of granulocyte-macrophage colony-stimulating factor to support dose-intensive chemotherapy.
OBJECTIVE
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.


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 degrees 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 micrograms/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 less than 300/microL) was 500 micrograms/m2 given CIV. Duration of leukopenia was 5.9 days compared with 13.2 and 10.2 days in the controls (P less than .05). The optimum regimens for shortening duration of hospitalization, however, were 500 and 750 micrograms/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 less than .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.
Neidhart
J A
JA
Department of Medicine, University of New Mexico Cancer Center, Albuquerque 87131-5636.
Mangalik
A
A
Stidley
C A
CA
Tebich
S L
SL
Sarmiento
L E
LE
Pfile
J E
JE
Oette
D H
DH
Oldham
F B
FB
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001772:Blood Cell Count; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous; D007970:Leukopenia / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012107:Research Design; D016896:Treatment Outcome
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor