Pharmacologic rationale for early G-CSF prophylaxis in cancer patients and role of pharmacogenetics in treatment optimization

The use of recombinant human granulocyte colony stimulating factors (G-CSF) has become an integral part of supportive care during cytotoxic chemotherapy. Current guidelines recommend the use of G-CSF in patients with substantial risk of febrile neutropenia. However, little consensus exists about optimal timing and tailoring of this therapy. Based on the known effects of chemotherapy and G-CSF on bone marrow compartments, we propose a model that supports the prophylactic rather than therapeutic use of G-CSF therapy. In addition, several genetic alterations in G-CSF signalling pathway have been described. These genetic variants may predict the risk of febrile neutropenia and response to G-CSF. Thus, future pharmacogenetic/omics studies in this field are warranted. Through the identification of patients at risk and the knowledge of biological basis for optimal timing, hopefully we should soon be able to improve the application of the existing guidelines for G-CSF therapy and patient's prognosis.