Granulocyte colony-stimulating factor stimulates recovery of granulocytes in patients receiving dose-intensive chemotherapy without bone marrow transplantation.

Abstract

Bone marrow colony-stimulating factors (CSF) ameliorate hematologic toxicity of standard chemotherapy regimens and may allow relatively safe use of intensive and more efficacious doses of anticancer drugs. Twenty-four patients with cancers for which no standard regimens were likely to be effective received repeated courses of a combination of cisplatin (150 mg/m2), etoposide (1,500 mg/m2), and cyclophosphamide (5,000 mg/m2) at doses for which bone marrow transplantation is usually used. A total of 10 patients received escalating doses of recombinant human granulocyte CSF (rhG-CSF); 11 patients receiving identical chemotherapy and supportive therapy without rhG-CSF served as controls for the first cycle of therapy. Five of these patients and 3 additional patients also served as their own controls, receiving rhG-CSF for all cycles after the first. No patient received bone marrow transplantation. rhG-CSF shortened the median duration of severe granulocytopenia (less than or equal to 100/mm3) in a dose-related fashion (P less than .03; Kruskal-Wallis test). Patients not receiving rhG-CSF had a median of 8.5 days of granulocytopenia. Those receiving 40 micrograms/kg of rhG-CSF for approximately 20 days from the third day after chemotherapy had a median of 7.0 days (P less than .23) and those receiving 60 micrograms/kg had a median of 5.5 days (P less than .007) of granulocytopenia. An rhG-CSF dose of 20 micrograms/kg had no effect. Recovery to a granulocyte count of at least 500/mm3 took a median of 12 days in the control group and 8 days (P less than .03) in patients receiving rhG-CSF at a dose of 60 mg/kg. The duration of antibiotic therapy (a median, 9.0 days v 5.0 days) was shortened with the two higher and effective doses of rhG-CSF compared with control patients. The duration of hospitalization (median of 20 days v 19 days) was not shortened. These findings that rhG-CSF decreases the risk of granulocytopenia associated with this particular dose-intensive chemotherapy regimen therapy administered without bone marrow transplantation.

G-CSF (Granulocyte-Colony Stimulating Factor) in the Central Nervous System

“…20,21 Soon after cloning of G-CSF its clinical potential was realized to counteract chemotherapy-induced neutropenia. [22][23][24] Today, G-CSF has been given to over three million patients worldwide for this and related indications such as bone-marrow harvesting, idiopathic neutropenias, and appears as a well-tolerated drug.…”

The combination of granulocyte colony-stimulating factor and stem cell factor significantly increases the number of bone marrow–derived endothelial cells in brains of mice following cerebral ischemia

“…Although G-CSF has been used in many patients to counter the side effects of chemotherapy as well as to prepare donors for peripheral cell harvesting, some concerns regarding its long-term safety still remain. [2][3][4] G-CSF may have several beneficial effects in animals with stroke. 5,6 Thus, it was reported that rats treated with G-CSF following middle cerebral artery occlusion (MCAO) have smaller infarcts and better functional outcome compared with controls.…”

O G-CSF na terapia do acidente vascular cerebral

“…15,23,29 Atualmente ele é utilizado para tratar neutropenia induzida por agentes quimioterápicos, ou no transplante de medula óssea. [23][24][25][30][31][32][33] O G-CSF é uma droga liberada pelo FDA e pelo Ministério da Saúde no Brasil, tendo já sido administrada a milhões de pacientes em todo o mundo, e é bem tolerada pelo organismo humano. Mais recentemente, tem sido demonstrada uma surpreendente atividade do G-CSF no SNC, 13,17,20,22,[34][35][36][37][38] fato que adiciona um potencial regenerativo em várias doenças neurológicas.…”