Phase I study of granulocyte colony-stimulating factor in patients with transitional cell carcinoma of the urothelium.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered at a dose of 1-60 micrograms/kg of body weight to 22 patients with transitional cell carcinoma before chemotherapy as part of a Phase I/II study. In all patients, a specific dose-dependent increase in the absolute neutrophil count (ANC) of 1.8-12 fold was seen. In addition, this augmentation in the ANC was accompanied by an increase in leukocyte alkaline phosphatase, a marker of secondary granule formation. In six of eight patients analyzed, an increase in bone marrow myeloid to erythroid cell ratio was seen. Day 14 peripheral blood cell derived colony forming unit granulocyte macrophage were also increased by day 6 of rhG-CSF treatment. Circulating levels of eosinophils and basophils were unchanged; however, a 10-fold increase in monocytes was observed in patients treated at the highest doses. There was also a small increase in CD3+ lymphocytes that was not dose dependent. Hemoglobin, hematocrit, and platelet count remained near baseline throughout the period of rhG-CSF administration. These findings demonstrate that rhG-CSF is a potent stimulus for normal neutrophil proliferation and maturation.
Gabrilove
J L
JL
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York 10021.
Jakubowski
A
A
Fain
K
K
Grous
J
J
Scher
H
H
Sternberg
C
C
Yagoda
A
A
Clarkson
B
B
Bonilla
M A
MA
Oettgen
H F
HF
D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004341:Drug Evaluation; D016179:Granulocyte Colony-Stimulating Factor; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D014565:Urogenital Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor