Colony-Stimulating Factors Shorten Severe Neutropenia

Colony-Stimulating Factors Shorten Severe Neutropenia

Neutrophil counts drop less and recover faster in chemotherapy patients who take colony-stimulating factors (CSFs), said George Demetri, MD, at the 6th International Symposium on Supportive Care in Cancer. Agents such as G-CSF [granulocyte colony-stimulating factor] and GM-CSF [granulocyte-macrophage colony-stimulating factor] can, in dose-dependent fashion, raise the circulating leukocyte counts in humans, with remarkably few toxicities, said Dr. Demetri, who is Assistant Professor of Medicine at Harvard Medical School and Staff Physician in the Division of Medical Oncology at the Dana Farber Institute, both in Boston.

He said CSFs might be used clinically in three ways. They might be used to prevent infections in patients who have not yet had one (primary prophylaxis), they might be used to prevent recurrence of infection (secondary prophylaxis), or they might be used during an infection (treatment). Most research has focused on the use of CSFs in primary prophylaxis.

Dr. Demetri reviewed randomized placebo-controlled trials of these agents. Studies consistently show that neutrophil counts drop below 500 per cubic millimeter in both patients treated with CSFs and those who get placebos. However, those treated with CSF hit their nadir about a day sooner than control patients and their nadir is not quite as low. Also, neutrophil counts bounce back above 500 per cubic millimeter in half the time in CSF-treated patients. As a result, says Dr. Demetri, the total time spent at risk for an infection is only half as long as it would have been if the patient had not gotten the CSF.

In the clinic, he continued, you can show a markedly reduced incidence of fever with neutropenia in the first cycle. But many questions still remain unanswered. For example, the threshold dose for clinical effectiveness is unknown; perhaps doses lower than today's arbitrary standard of 5 mcg/kg/day would be effective. Nor is it clear how long one should should wait after chemotherapy before administering the CSF dose.

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

Until guidelines for use are studied and accepted, Dr. Demetri said that it's reasonable to use CSFs for primary prophylaxis when patients are receiving strongly myelosuppressive chemotherapy regimens or are getting bone-marrow transplants.

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