Neutropenia—the lowering of the white blood cells that fight infections—is a major dose-limiting side effect of systemic cancer chemotherapy. Neutropenia with fever, or febrile neutropenia, often requires hospitalization for further evaluation and the administration of broad-spectrum antibiotics. In addition to negatively impacting the patient's quality of life, such complications can result in chemotherapy delays or dose reductions, which may compromise clinical outcomes.
Neutropenia-the lowering of the white blood cells that fight infections-is a major dose-limiting side effect of systemic cancer chemotherapy. Neutropenia with fever, or febrile neutropenia, often requires hospitalization for further evaluation and the administration of broad-spectrum antibiotics. In addition to negatively impacting the patient's quality of life, such complications can result in chemotherapy delays or dose reductions, which may compromise clinical outcomes.
While prophylactic use of colony-stimulating factors (CSFs) may diminish the risk and duration of severe neutropenia, CSFs are not used routinely in patients at risk of neutropenia because of their high cost. To enhance patient care by assisting clinicians in the appropriate preventative use of CSFs, experts from the National Comprehensive Cancer Network (NCCN) have released new practice guidelines. They apply to all patients, whether they are receiving cancer curative or supportive regimens, said Douglas Blayney, M.D., medical director at University of Michigan Comprehensive Cancer Center, Ann Arbor, Mich., and a member of the NCCN Myeloid Growth Factors Panel.
The guidelines first assess the risk for chemotherapy-associated neutropenia. Components include the type of cancer and chemotherapy regimen, patient-related factors, and treatment intent. "Intervention strategies urge the use of CSFs, such as filgrastim [Neupogen, Amgen] and pegfilgrastim [Neulasta, Amgen], in the prevention of chemotherapy-induced neutropenia," stated Robert Adamson, Pharm.D., director of clinical pharmacy services at Saint Barnabas Health Care System corporate offices in Livingston, N.J.
The decision of the NCCN panel to use the 20% cutoff is based on a series of studies, said Jeffrey Crawford, M.D., chief of medical oncology and associate director of clinical research, Duke Comprehensive Cancer Center in Durham, N.C., and chair of the NCCN panel. In a study published in the Journal of Clinical Oncology in 2002, the use of filgrastim reduced the febrile neutropenia rate to 18%, compared with 38% in the group that did not receive growth factor support. The most noteworthy study finding was that in patients receiving pegfilgrastim, the incidence of febrile neutropenia was even lower-at 9%. The largest trial to date evaluating the use of prophylactic CSFs, reported in the Journal of Clinical Oncology in 2005, showed that the incidence of febrile neutropenia was reduced to 1% in the pegfilgrastim group, compared with 17% in the placebo group.
Pharmacists should be aware of the chemotherapy regimens associated with a high risk of febrile neutropenia, noted Adamson, and should work in conjunction with physicians to ensure that prophylactic CSFs are appropriately initiated in patients who will be receiving these chemotherapeutic agents. Among the regimens listed in the NCCN guidelines, high doses of cyclophosphamide or the use of etoposide in patients with non-Hodgkin's lymphoma and high doses of anthracycline agents (i.e., doxorubicin) in early-stage breast cancer patients have been identified as significant febrile neutropenia predictors. It is practically impossible to accomplish dose-dense therapy, where high-dose chemotherapy is administered every two weeks, without the support of prophylactic myeloid growth factors, Adamson said.
The guidelines give a prior history of severe or febrile neutropenia with similar chemotherapy regimens as a risk factor for delaying full-dose treatment and developing subsequent febrile neutropenia. Additional risk factors for developing febrile neutropenia include age greater than 65 years, female gender, and poor nutritional status.
Both filgrastim and pegfilgrastim are Food & Drug Administration-approved for the prevention of chemotherapy-induced neutropenia. The new guidelines recommend initiating filgrastim daily, starting one to three days after chemotherapy begins, at a dose of 5 mcg/kg/day and continued until the post-nadir absolute neutrophil count (ANC) recovery is normal or near-normal by laboratory standards. Data also support the use of pegfilgrastim 24 hours after completion of chemotherapy, given every three weeks in one dose of 6 mg per cycle of treatment.