We evaluated the ability of human recombinant granulocyte colony-stimulating factor (rhG-CSF) to prevent chemotherapy-induced neutropenia or to accelerate recovery from this complication and thus allow patients to receive full doses of antineoplastic agents on time, according to protocol design. Twenty-seven patients with transitional-cell carcinoma of the urothelium who were undergoing treatment with methotrexate, doxorubicin, vinblastine, and cisplatin were given rhG-CSF (up to 60 micrograms per kilogram of body weight per day) before their first cycle of combination chemotherapy, during the first cycle, or at both points. Treatment with rhG-CSF before chemotherapy resulted in a dose-dependent increase in the absolute neutrophil count. Treatment with rhG-CSF after chemotherapy significantly reduced the number of days (91 percent) per patient on which the absolute neutrophil count was 1000 per microliter or less (P = 0.0039), reduced the number of days (1 vs. 35) on which antibiotics were used to treat fever and neutropenia, and significantly increased the percentage (100 vs. 29 percent) of patients qualified to receive planned chemotherapy on day 14 of the treatment cycle (P = 0.0015). In addition, the incidence of mucositis was significantly decreased (11 vs. 44 percent, P = 0.041), as was its severity. These findings demonstrate that rhG-CSF is a potent stimulus of normal neutrophil proliferation and maturation. In addition, its administration can reduce both the hematopoietic and oral toxicity of chemotherapy.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered at a dose of 1-60 ,g/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 niear baseline throughout the period of rhG-CSF administration. These findings demonstrate that rhG-CSF is a potent stimulus for normal neutrophil proliferation and maturation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.