Recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy: a phase Ib trial.
We evaluated the toxic, hematopoietic, and immunomodulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). The rHuGM-CSF was administered at doses up to 50 micrograms/kg by daily 2-hour intravenous infusions to 11 patients with advanced malignancy. It induced dose-related increases in cells of the myeloid series, but it had no significant effect on reticulocyte or platelet counts. Bone marrow cellularity increased with higher doses of rHuGM-CSF, but there was a dose-related decrease in the number of colony-forming units--granulocyte-monocyte--and colony-forming units--granulocyte-erythrocyte-monocyte-megakaryocyte--per 10(5) bone marrow cells. The rHuGM-CSF caused transient increased expression of CD11b and CD16 on granulocytes but increased expression of HLA-DR and decreased expression of the high-affinity Fc receptor on monocytes and no change in monocyte production of H2O2. Thus, rHuGM-CSF has potent effects on granulocyte, eosinophil, and monocyte numbers in the peripheral blood and bone marrow. In addition, it enhances the expression of monocyte and granulocyte activation-associated surface markers.
Steis
R G
RG
Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research Facility, MD 21701.
VanderMolen
L A
LA
Longo
D L
DL
Clark
J W
JW
Smith
J W
JW
Kopp
W C
WC
Ruscetti
F W
FW
Creekmore
S P
SP
Elwood
L J
LJ
Hursey
J
J
D000943:Antigens, Differentiation / Q000032:analysis; D001772:Blood Cell Count; D001853:Bone Marrow / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000009:adverse effects / Q000627:therapeutic use*; D004341:Drug Evaluation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology; D006133:Growth Substances / Q000009:adverse effects / Q000627:therapeutic use*; D006684:HLA-DR Antigens / Q000032:analysis; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D016177:Macrophage-1 Antigen; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009369:Neoplasms / Q000628:therapy*; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
D000943:Antigens, Differentiation; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D006684:HLA-DR Antigens; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D017452:Receptors, IgG; D016028:Receptors, Leukocyte-Adhesion; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor