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.