Filgrastim (r-metHuG-CSF): the first 10 years.

I T HAS BEEN KNOWN for at least three decades that very specific factors control hematopoiesis, acting on early cells in the hematopoietic system to produce mature, functional cells. The isolation, purification, and cloning of these factors has lead to a new class of therapeutic agents, including the colony-stimulating factors and interleukins. This review is devoted to granulocyte colony-stimulating factor (G-CSF), specifically Filgrastim (r-metHuG-CSF), the bacterially synthesized recombinant protein form of GCSF, that acts on neutrophils, the body's major defense against infections. The purification and molecular cloning of Filgrastim were performed between 1984 and 1986,L-3 and the clinical development of Filgrastim commenced in 1986, with approval for clinical use in cancer patients treated with chemotherapy4" obtained in the United States in February 1991. In the 5 years since its approval, 1.2 million patients have been treated with Filgrastim (Amgen [Thousand Oaks, CA], data on file). Filgrastim was initially used as an adjunct to chemotherapy for ameliorating neutropenia, one of the major side effects of cancer chemotherapy. Its use has led to reduced infections and hospital admissions for patients with cancer. Besides chemotherapy-induced neutropenia, Filgrastim has been approved in more than 70 countries for the treatment of myelosuppression after bone marrow transplantation, severe chronic neutropenia (SCN), acute leukemia, aplastic anemia (AA), myelodysplastic syndromes (MDS), and mobilization of peripheral blood progenitor cells (PBPCs) for transplantation. The use of Filgrastim has made possible delivery of full-dose chemotherapy and high-dose chemotherapy and has benefited patients who are immunocompromised. A second form of rHuG-CSF (lenograstim) received approval in Europe in 1993. The biologic properties of Filgrastim and lenograstim are similar and are given in Table 1. This review focuses on Filgrastim and reviews the first 10 years of clinical development and the first 5 years of postapproval use as well as additional potential clinical applications.