A comparative review of colony-stimulating factors

The efficacy of dose-intensive chemotherapy in oncology is limited by the duration and severity of neutropenia. Several recombinant DNA factors that alter neutrophil proliferation and function, and are characterised by their ability to stimulate colony formation of myeloid progenitors in vitro, have been shown to alter clinical sequelae associated with neutropenia in vivo. Two of these factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been approved by the US FDA. One other factor, macrophage colony-stimulating factor (M-CSF), is approved as indicated therapy in Japan. The clinical effects of these agents are compared in this review. Results of clinical trials suggest that the efficacy of G-CSF is greatest when used as an agent to enhance circulation of stem cells and pre-colony-forming progenitor cells. It is also an effective agent in reducing the duration of neutropenia following dose-intensive chemotherapy, thereby leading to a reduction in the incidence of febrile neutropenia. Similar observations were made with GM-CSF, although toxicity with the latter agent appears to be moderately greater than that observed with G-CSF. Functional activity of GM-CSF is broader than that of G-CSF, in that macrophages are affected by GM-CSF. As a result, some data suggest that GM-CSF may be more applicable to patients with a high risk of infection. There is a suggestion that M-CSF assists neutrophil recovery, although this effect may be indirect, via the induction of other cytokines. The predominant effect of M-CSF appears to be enhancement of macrophage and monocyte function, which may reduce the severity and duration of fungal infection.