Colony-Stimulating Factors Shorten Severe Neutropenia

Neutrophil counts drop less and recover faster in chemotherapypatients who take colony-stimulating factors (CSFs), said GeorgeDemetri, MD, at the 6th International Symposium on SupportiveCare in Cancer. Agents such as G-CSF [granulocyte colony-stimulatingfactor] and GM-CSF [granulocyte-macrophage colony-stimulatingfactor] can, in dose-dependent fashion, raise the circulatingleukocyte counts in humans, with remarkably few toxicities, saidDr. Demetri, who is Assistant Professor of Medicine at HarvardMedical School and Staff Physician in the Division of MedicalOncology at the Dana Farber Institute, both in Boston.

He said CSFs might be used clinically in three ways. They mightbe used to prevent infections in patients who have not yet hadone (primary prophylaxis), they might be used to prevent recurrenceof infection (secondary prophylaxis), or they might be used duringan infection (treatment). Most research has focused on the useof CSFs in primary prophylaxis.

Dr. Demetri reviewed randomized placebo-controlled trials of theseagents. Studies consistently show that neutrophil counts dropbelow 500 per cubic millimeter in both patients treated with CSFsand those who get placebos. However, those treated with CSF hittheir nadir about a day sooner than control patients and theirnadir is not quite as low. Also, neutrophil counts bounce backabove 500 per cubic millimeter in half the time in CSF-treatedpatients. As a result, says Dr. Demetri, the total time spentat risk for an infection is only half as long as it would havebeen if the patient had not gotten the CSF.

In the clinic, he continued, you can show a markedly reduced incidenceof fever with neutropenia in the first cycle. But many questionsstill remain unanswered. For example, the threshold dose for clinicaleffectiveness is unknown; perhaps doses lower than today's arbitrarystandard of 5 mcg/kg/day would be effective. Nor is it clear howlong one should should wait after chemotherapy before administeringthe CSF dose.

The American Society of Clinical Oncology recently published theirguidelines for use of CSFs. Insurance companies and drug companiesalso all working on guidelines. The financial ramifications ofguidelines could be significant.

Until guidelines for use are studied and accepted, Dr. Demetrisaid that it's reasonable to use CSFs for primary prophylaxiswhen patients are receiving strongly myelosuppressive chemotherapyregimens or are getting bone-marrow transplants.