Phase I study of granulocyte colony-stimulating factor in patients with transitional cell carcinoma of the urothelium

• Published in: The Journal of clinical investigation 1988-10, Vol.82 (4), p.1454-1461
• Main Authors: GABRILOVE, J. L, JAKUBOWSKI, A, ALTON, K, BOONE, T, ALTROCK, B, WELTE, K, SOUZA, L, FAIN, K, GROUS, J, SCHER, H, STERNBERG, C, YAGODA, A, CLARKSON, B, BONILLA, M. A, OETTGEN, H. F
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Bone Marrow - pathology; Carcinoma, Transitional Cell - blood; Carcinoma, Transitional Cell - drug therapy; Carcinoma, Transitional Cell - pathology; Colony-Forming Units Assay; Colony-Stimulating Factors - adverse effects; Colony-Stimulating Factors - pharmacokinetics; Colony-Stimulating Factors - therapeutic use; Drug Evaluation; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells - pathology; Humans; Leukocyte Count - drug effects; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Neutrophils - pathology; Recombinant Proteins - adverse effects; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - therapeutic use; Tumors of the urinary system; Urinary tract. Prostate gland; Urogenital Neoplasms - blood; Urogenital Neoplasms - drug therapy; Urogenital Neoplasms - pathology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI113751

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.