Hematopoietic growth factors in the reduction of chemotherapeutic toxicity

Neutropenia is the most common dose-limiting toxicity of conventional chemotherapy. The colony-stimulating factors (CSFs), granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF, stimulate proliferation and maturation of myeloid progenitors and have been effective in reducing neutropenia and its complications. The primary use of CSFs in patients receiving chemotherapy for small cell lung cancer has resulted in a reduction in the incidence of febrile neutropenia, a decrease in the duration of grade IV neutropenia, and a reduction in hospitalization time and antibiotic use. Although CSF use allows for higher dose intensity, a survival benefit has not been proven. The use of CSFs after the occurrence of neutropenic fever decreases the duration of grade IV neutropenia, but effects on hospitalization and antibiotic use are less well-defined. The therapeutic use of CSFs in the setting of established neutropenia, regardless of the presence or absence of fever, is not supported in the literature. The administration of CSFs to patients with acute myeloid leukemia is safe in that no trial has demonstrated evidence of leukemic stimulation with these drugs. As in other settings, the duration of neutropenia is shortened if CSFs are used postchemotherapy with evidence of clinical benefit. CSFs also decrease chemotherapeutic toxicity via other mechanisms. The use of G-CSF reduces the incidence of mucositis, in normal donors enhances the yield of leukapheresis for granulocyte transfusion, and is beneficial in the autologous transplant setting. These effects of CSFs in mitigating chemotherapeutic toxicity are reviewed.