Filgrastim for Chemotherapy-Induced Neutropenia
Filgrastim should be initiated 24-72 hours after completing chemotherapy at 5 mcg/kg/day subcutaneously and continued daily until the absolute neutrophil count (ANC) recovers to 2,000-3,000/mm³—not higher. 1, 2, 3
Primary Prophylaxis Indications
Use filgrastim prophylactically when the chemotherapy regimen carries >20% risk of febrile neutropenia. 1, 2 This threshold is the clearest evidence-based cutoff for routine prophylaxis. 1
For regimens with 10-20% risk of febrile neutropenia, add filgrastim if patient-specific risk factors are present, including: 1, 4
- Age ≥65 years 2, 4
- Prior febrile neutropenia episode 1
- Advanced disease stage 1
- Poor performance status 4
- Curative or adjuvant treatment intent where dose reductions would compromise survival 1
Dosing and Administration Protocol
Standard dose: 5 mcg/kg/day subcutaneously 1, 2, 3, 5
Timing: Start 24-72 hours (1-3 days) after the last chemotherapy dose—never on the same day as chemotherapy. 1, 2, 3 Administering filgrastim within 24 hours of chemotherapy significantly increases the risk of severe thrombocytopenia and paradoxically worsens febrile neutropenia. 1, 3
Duration: Continue daily injections until post-nadir ANC reaches 2,000-3,000/mm³. 2, 3 A common pitfall is continuing treatment until ANC exceeds 10,000/mm³—this is unnecessary and should be avoided. 1, 2, 3
Route: Subcutaneous administration is standard. 1, 3 The dose may be rounded to the nearest vial size based on institution-defined weight limits. 1
Alternative: Pegfilgrastim
Pegfilgrastim offers equivalent efficacy with simplified dosing: a single 6 mg subcutaneous injection once per chemotherapy cycle, administered 24 hours after completing chemotherapy. 1, 3, 6 Both filgrastim and pegfilgrastim are Category 1 recommendations. 1
Do not use the 6 mg fixed dose in patients weighing <45 kg. 3 For weekly chemotherapy regimens, daily filgrastim is more appropriate than long-acting pegfilgrastim. 6
Therapeutic Use in Established Febrile Neutropenia
Filgrastim does not reduce mortality in febrile neutropenia but consistently shortens neutropenia duration and hospitalization length. 2 Consider adding filgrastim 5 mcg/kg/day to antibiotics only in high-risk febrile neutropenia with: 2
- Severe neutropenia (ANC <100/mm³) 2, 7
- Anticipated prolonged neutropenia (>7-10 days) 2
- Sepsis syndrome or multiorgan dysfunction 2
- Pneumonia or invasive fungal infection 2
- Age >65 years 2
In the landmark trial, filgrastim reduced median neutropenia duration from 4 to 3 days and time to resolution of febrile neutropenia from 6 to 5 days, but did not reduce fever duration. 7 The benefit was greatest in patients with documented infection and presenting ANC <100/mm³. 7
Critical Contraindications
Absolute contraindication: Do not administer filgrastim during concurrent chest/thoracic radiotherapy. 1, 2, 3 This combination significantly increases complications and mortality. 1, 3
Do not give filgrastim to patients without neutropenia, especially those with community- or hospital-acquired pneumonia. 1, 2 Colony-stimulating factors should be avoided in infections unrelated to neutropenia. 1
Do not use routinely in pediatric acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) due to theoretical concerns about stimulating leukemic blast growth. 2, 3
Secondary Prophylaxis After Neutropenic Events
If a patient develops febrile neutropenia or dose-limiting neutropenia during a chemotherapy cycle, they are now high-risk for subsequent cycles. 1 Add filgrastim prophylaxis for all remaining cycles at the same chemotherapy dose and schedule. 1
If febrile neutropenia occurs despite filgrastim prophylaxis, reduce chemotherapy dose or change the regimen—unless this would compromise survival. 1
Special Populations
Acute Myeloid Leukemia: Filgrastim reduces median severe neutropenia duration from 19 to 14 days following induction chemotherapy (5-day difference, p=0.0001). 5 Start 24 hours after completing chemotherapy and continue until ANC ≥1,000/mm³ for 3 consecutive days or ≥10,000/mm³ for 1 day, maximum 35 days. 5
Stem Cell Transplantation: Initiate filgrastim 5 mcg/kg/day starting day 1 post-transplant, with dose adjustments based on ANC recovery. 2 In allogeneic transplant, filgrastim may be safely delayed until day 5-7 post-transplant. 3
Renal or Hepatic Impairment: No dose adjustment necessary. 5
Common Pitfalls to Avoid
Starting too late: In community practice, filgrastim was often initiated 7.7 days after chemotherapy (first cycle) and 4.9 days in subsequent cycles—far later than the recommended 1-3 days. 8 This delayed initiation reduces effectiveness.
Insufficient duration: Community practice showed filgrastim administered for only 3.7-5.2 days on average, 8 whereas clinical trials demonstrate 10-14 days is typically needed until neutrophil recovery. 1, 6
Targeting excessive ANC: Stop filgrastim when ANC reaches 2,000-3,000/mm³; continuing to ANC >10,000/mm³ provides no additional benefit. 1, 2, 3
Concurrent radiotherapy: Never combine with chest radiotherapy due to increased mortality. 1, 2, 3
Comparative Effectiveness
In a large observational study of 2,863 patients in community practice, pegfilgrastim users had 4.7% incidence of febrile neutropenia versus 6.5% with filgrastim (adjusted OR 1.41, p=0.040). 8 This difference likely reflects better adherence with single-dose pegfilgrastim and more appropriate timing (initiated 2.4 days post-chemotherapy versus 9.6 days for filgrastim). 8