ASCO updates guidelines on use of CSFs

September 18, 2006

The American Society of Clinical Oncology (ASCO) recently updated its guidelines for the use of hematopoietic colony-stimulating factors (CSFs). The 2005 update committee unanimously agreed that the reduction in febrile neutropenia (FN) was an important clinical outcome that justified the use of CSFs, regardless of impact on other factors, when the risk of FN was approximately 20% and no other equally effective regimen that did not require CSFs was available. The first guidelines were published in 1994, and they were updated in 1996, 1997, 2000, and, most recently, 2005.

Prophylactic therapy with CSFs may reduce the probability of FN-the most common presentation of infection in patients receiving chemotherapy. There are two main types of CSFs: granulocyte colony-stimulating factor (G-CSF), which includes filgrastim (Neupogen, Amgen) and pegfilgrastim (Neulasta, Amgen), and granulocyte-macrophage colony-stimulating factor (GM-CSF). An example of a GM-CSF is sargramostim (Leukine, Berlex).

The ASCO CSF update committee does not recommend or oppose any chemotherapy regimen. "Primary prophylaxis with CSFs is recommended for patients receiving chemotherapy with a risk of developing FN of 20% or more, compared with 40% in the previous guidelines," said Stacy Shord, Pharm.D., BCOP, assistant professor of pharmacy practice at the University of Illinois at Chicago College of Pharmacy.

The updated guidelines recommend secondary prophylaxis with CSFs for patients who experienced a neutropenic complication from a prior cycle of chemotherapy (for which primary prophylaxis was not received), in which dose reduction may compromise disease-free or overall survival or treatment outcome. However, based on available data, no conclusions can be made regarding the benefits of secondary prophylaxis on survival, cost, and quality of life.

The impact of CSFs on the disease has been small and does not routinely warrant their use to improve survival. However, CSFs significantly reduce the risk of FN, which is the basis for the committee's recommendation. A meta-analysis of prophylactic CSF use in patients with solid tumors or malignant lymphoma has shown significant reductions in the risk of infection, from 37% to 20%, and the risk of infection-related mortality, from 3.3% to 1.7%. Another meta-analysis of non-Hodgkin's lymphoma and Hodgkin's disease patients found that patients who received prophylactic CSFs had significant reductions in the relative risk of severe neutropenia, FN, and infection, compared with patients who did not receive prophylactic therapy.

The ASCO guidelines are not intended to supplant physician judgment with respect to particular patients or specific situations, and ASCO considers adherence to these guidelines to be voluntary. "Even though our institution does not have a set protocol, most of our physicians will follow these guidelines as there are new studies supporting the use of CSFs in primary FN prevention," stated Sachin Shah, Pharm.D., BCOP, assistant professor of pharmacy practice in hematology and oncology at the Texas Tech University Health Sciences Center School of Pharmacy. He is also a clinical pharmacist for the VA North Texas Healthcare System.

According to the guidelines, patients under 65 with diffuse aggressive lymphoma receiving the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen or more aggressive regimens should receive CSFs to reduce the incidence of FN and infection. Patients who are over 65 and have a performance status of two or more are at increased risk of FN. The prophylactic use of CSFs in the elderly was studied in several trials of patients who received CHOP or CHOP-like chemotherapy. Three studies showed a reduced risk of FN or infection by more than 50% in people who received G-CSF.

In the pediatric population, the use of CSFs is usually guided by clinical protocols. CSFs are reasonable for primary prophylaxis in pediatric patients who have a likelihood of FN. However, the use of secondary prophylaxis should be limited to high-risk patients. CSFs in children with acute lymphocytic leukemia should be used with caution due to the potential risk of developing secondary myeloid leukemia or myelodysplastic syndrome.