Pharmacology: Colony-stimulating factors are glycoprotein which acts on haematopoietic cells by binding to specific cell surface receptors and stimulating proliferation, differentiation commitment, and some end-cell functional activation. Endogenous G-CSF is a lineage specific colony-stimulating factor which is produced by monocytes, fibroblasts, and endothelial cells. FILGRASTIM (LEUCOGEN) contains r-metHuG-CSF, which regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation, differentiation, and selected end-cell functional activation (including enhanced phagocytic ability, priming of the cellular metabolism associated with respiratory burst, antibody dependent killing and the increased expression of some functions associated with cell surface antigens). G-CSF Is not species specific and has been shown to have minimal direct in vivo or in vitro effects on the production of haematopoietic cell types other than the neutrophil lineage.
Cancer Patients Receiving Myelosuppressive Chemotherapy: Neutropenia and infection are major dose-limiting side effects of chemotherapy. The risk of initial infection and subsequent complications is directly related to the depth and duration of neutropenia. The magnitude of neutropenia is dependent on the intensity of the chemotherapy regimen. Filgrastim has been shown to be safe and effective in accelerating the recovery of neutrophil counts following a variety of chemotherapy regimens. The benefits of therapy were shown to be prevention of infection as manifested by febrile neutropenia, decreased hospitalization, and decreased antibiotic usage. No difference in survival or disease progression was demonstrated.
Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy: Essentially, all patients with Acute Myeloid Leukemia receiving induction therapy, and most such patients receiving intensive, post remission consolidation therapy, develop fevers requiring hospitalization and intravenous antibiotics until neutrophil recovery occurs. Treatment with Filgrastim significantly reduced the median time to Absolute Neutrophil Counts (ANC) recovery and the median duration of fever, antibiotic use and hospitalization following induction chemotherapy. There are no reports of Filgrastim effects related with complete remission rate, disease-free survival, time to progression, or overall survival.
Cancer Patients Receiving Bone Marrow Transplant: The major complications of high-dose chemotherapy supported by autologous bone marrow transplant (BMT) are disease recurrence, infection, the need for red blood cell and platelet transfusions, delayed or incomplete engraftment, organ damage from the ablative regimen, prolonged hospitalization, and high cost treatment. These same problems plus graft-versus host disease and graft rejection are also present in patients undergoing allogenic BMT in anticipation of reducing the severity of infectious complications, thereby decreasing hospitalization time, reducing costs and improving quality of life.
Peripheral Blood Progenitor Cell Collection and Therapy in Cancer Patients: The mobilization of peripheral blood progenitor cells (PBPC) substitutes the autologous BMT. The major adverse reactions associated with the procedure are reduction in the platelet numbers and other haematopoietic elements. Use of Filgrastim to mobilize PBPC into the circulation for harvesting is expected to enhance progenitor numbers, lessen the frequency, duration and cost of leukapheresis procedures, potentially speed hematological recovery after transplantation of the CSF-mobilized cells and reduce the hospitalization.
Patients with Severe Chronic Neutropenia: Severe chronic neutropenia (SCN) (idiopathic, cyclic and congenital) is characterized by a selective decrease in the number of circulating neutrophils and an enhanced susceptibility to bacterial infections. The administration of Filgrastim has been shown to be safe and effective in causing a sustained increase in the neutrophil count and a decrease in infectious morbidity in treated patients.