Neutrophil growth factors.
A significant advance in the field of neutrophil growth factors has occurred with the commercial availability of pegfilgrastim (Neulasta, Amgen, Thousand Oaks, CA), a new-generation, pegylated filgrastim molecule with a sustained duration of action. Pegylation of filgrastim allows once-per-chemotherapy cycle frequency of administration, in contrast to repeated daily administration of filgrastim. Clinical data from two randomized trials demonstrate equivalence of pegfilgrastim and filgrastim in duration of severe neutropenia and recovery from absolute neutrophil count nadir following myelosuppressive chemotherapy. In addition, secondary endpoint results in both trials suggest an enhanced reduction in the overall incidence of febrile neutropenia with pegfilgrastim. Neutrophil kinetic studies demonstrate steady serum neutrophil levels following pegfilgrastim administration, in contrast to the peak-and-trough neutrophil effects observed following filgrastim administration. Granulocyte colony-stimulating factor (G-CSF) therapy has an antiapoptotic effect on neutrophils, which may be enhanced by continuous serum concentrations of pegfilgrastim. Monocytes possess a G-CSF receptor, and this finding has fueled investigational analysis of the role of G-CSF as a mediator in the host inflammatory response to foreign pathogens. The data demonstrate that depending on the timing of administration, G-CSF may function as a proinflammatory mediator or an anti-inflammatory mediator. It is likely that the early, prophylactic administration of pegfilgrastim creates an environment in which an anti-inflammatory response predominates. Additional investigational studies will be necessary to confirm and better define the mechanism for enhanced benefit of pegfilgrastim over filgrastim. The recent biologic findings of the mechanism of G-CSF therapy reviewed here provide a strong basis from which further research initiatives may be conducted.
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