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 fact ors that alter neutrophil proliferation and function, and are characte rised by their ability to stimulate colony formation of myeloid progen itors in vitro, have been shown to alter clinical sequelae associated with neutropenia in vivo. Two of these factors, granulocyte colony-sti mulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been approved by the US FDA. One other factor, m acrophage 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 effectiv e agent in reducing the duration of neutropenia following dose-intensi ve chemotherapy, thereby leading to a reduction in the incidence of fe brile neutropenia. Similar observations were made with GM-CSF, althoug h toxicity with the latter agent appears to be moderately greater than that observed with G-CSF. Functional activity of GM-CSF is broader th an that of G-CSF, in that macrophages are affected by GM-CSF. As a res ult, 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 assist s neutrophil recovery, although this effect may be indirect, via the i nduction of other cytokines. The predominant effect of M-CSF appears t o be enhancement of macrophage and monocyte function, which may reduce the severity and duration of fungal infection.