From the Guidelines
G-CSF should not be routinely used as adjunctive treatment with antibiotic therapy for patients with fever and neutropenia, but it should be considered in patients with high-risk features, such as expected prolonged and profound neutropenia, age greater than 65 years, uncontrolled primary disease, pneumonia, hypotension, and multiorgan dysfunction. The use of G-CSF in neutropenic fever is supported by guidelines from the Infectious Diseases Society of America and the American Society of Clinical Oncology, which recommend its use in patients at high risk for infection-related complications 1, 2.
High-Risk Features
The following high-risk features should be considered when deciding to use G-CSF:
- Expected prolonged (≥ 10 days) and profound (≤ 0.1 x 10^9/L) neutropenia
- Age greater than 65 years
- Uncontrolled primary disease
- Pneumonia
- Hypotension and multiorgan dysfunction (sepsis syndrome)
- Invasive fungal infection
- Hospitalization at the time of the development of fever
G-CSF Treatment
G-CSF treatment should be started immediately after the chemotherapy is completed, and it should be continued until the absolute neutrophil count recovers to above 1,000-1,500 cells/μL. The primary G-CSF medications include filgrastim (Neupogen) at 5 μg/kg/day subcutaneously, pegfilgrastim (Neulasta) as a single 6 mg dose, or biosimilar versions.
Monitoring and Side Effects
While using G-CSF, monitor for bone pain (the most common side effect), which can be managed with analgesics. Other potential side effects include mild elevations in lactate dehydrogenase, alkaline phosphatase, and uric acid levels. G-CSF significantly reduces the duration of neutropenia, risk of infection, length of hospitalization, and antibiotic use in febrile neutropenia patients, making it a valuable supportive care intervention 2.
Clinical Benefits
The clinical benefits of G-CSF accrue when the risk of neutropenic fever associated with a chemotherapy regimen is >20%, unless the treatment is symptomatic or palliative, in which cases dose reduction is usually appropriate 2. Primary prophylaxis—the use of CSFs for prevention in the first cycle of treatment for many solid tumors—does appear to reduce the incidence of fever and neutropenia and is likely to be most cost-effective.
From the FDA Drug Label
Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and some end-cell functional activation. Endogenous G-CSF is a lineage-specific colony-stimulating factor that is produced by monocytes‚ fibroblasts, and endothelial cells G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation‚ differentiation, and selected end-cell functions (including enhanced phagocytic ability‚ priming of the cellular metabolism associated with respiratory burst‚ antibody-dependent killing, and the increased expression of some cell surface antigens)
The role of Granulocyte-Colony Stimulating Factor (GCSF) in neutropenic fever is to:
- Stimulate the production of neutrophils within the bone marrow
- Enhance phagocytic ability and antibody-dependent killing of neutrophils
- Increase the expression of some cell surface antigens on neutrophils
- Regulate neutrophil progenitor proliferation and differentiation
This results in an increase in circulating neutrophil counts, which can help to prevent or treat neutropenic fever 3.
From the Research
Role of GCSF in Neutropenic Fever
- GCSF has proven efficacy in the prophylaxis of chemotherapy-induced neutropenia and is associated with a reduction in the duration of neutropenia, febrile neutropenia, hospitalisation, and intravenous antibiotic use 4.
- The use of G-CSF in the treatment of established neutropenia remains controversial, but a meta-analysis of randomised controlled trials demonstrated a reduction in prolonged hospitalisations 5.
- G-CSF treatment may offer substantial potential savings for hospitalised patients with established neutropenia over a wide range of model assumptions 5.
Clinical Benefits of GCSF
- G-CSF has been shown to reduce the incidence of febrile neutropenia, hospitalisation, and intravenous antibiotic use in patients with cancer 4, 5.
- Filgrastim, a form of G-CSF, has been shown to decrease the duration of fever, hospital stay, and antibiotic use in high-risk neuroblastoma patients 6.
- Pegfilgrastim, a sustained-duration form of filgrastim, has been shown to be as safe and effective as daily filgrastim in reducing the incidence of chemotherapy-induced neutropenia 4.
Economic Benefits of GCSF
- The use of G-CSF in the treatment of established neutropenia may reduce overall hospital costs by reducing the length of hospital stay and the need for antibiotics 5, 7.
- A pharmacoeconomic model suggested that therapeutic use of G-CSF should be considered for patients with established neutropenia to reduce overall hospital cost 5.
Pediatric Patients
- The use of G-CSF in pediatric patients with febrile neutropenia has been shown to reduce the duration of hospital stay and the need for antibiotics 7.
- Filgrastim and pegfilgrastim have been shown to be effective in reducing the occurrence of febrile neutropenia and infections in pediatric patients with cancer 6.