In vitro and in vivo analysis of the effects of recombinant human granulocyte colony-stimulating factor in patients.
Twelve patients with small cell lung cancer were treated with recombinant human granulocyte colony-stimulating factor, rhG-CSF, given by continuous infusion at doses ranging from 1 to 40 micrograms kg-1 day-1. Patients received the rhG-CSF before the start of intensive chemotherapy and after alternate cycles of chemotherapy. Several in vitro assays were performed using peripheral blood neutrophils and marrow progenitor cells collected from patients prior to and after infusion of the growth factor. Peripheral blood neutrophils were tested for mobility and phagocytic activity. In addition, in vitro clonogenic assays of marrow haemopoietic progenitor cells and analysis of bone marrow trephines and aspirates were carried out. We found that rhG-CSF in vivo has at least two main effects: (a) an early fall in peripheral neutrophils, within the first hour, followed by a rapid influx of mature neutrophils into the circulatory pool; (b) stimulation of proliferation and differentiation of neutrophil precursors in the bone marrow. Neutrophils released into the circulation were normal in tests of their mobility and phagocytic activity.
Bronchud
M H
MH
Department of Medical Oncology, Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Manchester, UK.
Potter
M R
MR
Morgenstern
G
G
Blasco
M J
MJ
Scarffe
J H
JH
Thatcher
N
N
Crowther
D
D
Souza
L M
LM
Alton
N K
NK
Testa
N G
NG
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002634:Chemotaxis, Leukocyte; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D004341:Drug Evaluation; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes; D006801:Humans; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000517:prevention & control; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D011994:Recombinant Proteins / Q000627:therapeutic use
D000970:Antineoplastic Agents; D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor