What are the differences between filgrastim (Granulocyte-Colony Stimulating Factor, G-CSF) and pegfilgrastim (pegylated G-CSF)?

Key Differences Between Filgrastim and Pegfilgrastim

Pegfilgrastim and filgrastim can both be used for the prevention of treatment-related febrile neutropenia, with the choice between them primarily depending on convenience, cost, and clinical situation. 1

Structural and Pharmacokinetic Differences

• Pegfilgrastim is a covalent conjugate of filgrastim with a 20 kDa polyethylene glycol (PEG) molecule attached to the N-terminus of the filgrastim protein 2
• The PEGylation significantly increases the terminal elimination half-life and decreases serum clearance of pegfilgrastim compared to filgrastim 3
• Filgrastim is primarily cleared by the kidneys, requiring daily administration, while pegfilgrastim is cleared by neutrophils in a self-regulating manner (cleared only after neutrophils start to recover) 2

Dosing and Administration

• Filgrastim requires daily subcutaneous injections (5 μg/kg/day) until neutrophil recovery, typically for 10-14 days per chemotherapy cycle 4, 1
• Pegfilgrastim is administered as a single fixed dose of 6 mg (or weight-based 100 μg/kg) per chemotherapy cycle 1, 5
• Pegfilgrastim should be administered 1-3 days after completion of chemotherapy, not on the same day as chemotherapy (although same-day administration may be acceptable in certain circumstances) 1
• For weekly chemotherapy regimens, daily G-CSFs like filgrastim may be more appropriate than long-acting formulations like pegfilgrastim 4

Clinical Efficacy

• A meta-analysis showed that pegfilgrastim is more effective than filgrastim at reducing the risk of febrile neutropenia (RR, 0.64; 95% CI, 0.43 to 0.98) 6, 1
• Both agents are similarly effective in reducing the duration of severe neutropenia in the first cycle of chemotherapy 3
• Pegfilgrastim may provide better neutrophil support in subsequent chemotherapy cycles compared to filgrastim 3
• For treatment of established neutropenia, filgrastim is preferred over pegfilgrastim due to its shorter half-life and ability to titrate the dose 4

Safety and Adverse Effects

• Both drugs have similar safety profiles and tolerability 3, 5
• Common adverse effects for both include bone pain, which can be managed with non-steroidal anti-inflammatory drugs 7
• The incidence of bone pain is similar between pegfilgrastim and filgrastim (RR = 0.95; 95% CI, 0.76-1.19) 6

Clinical Applications

• Both agents are indicated for reducing the duration of neutropenia and incidence of febrile neutropenia in patients receiving myelosuppressive chemotherapy 1, 4
• Filgrastim may be preferred for:
  • Weekly chemotherapy regimens 4
  • Treatment of established neutropenia 4
  • Stem cell mobilization for transplantation 1
  • Situations requiring dose titration 4
• Pegfilgrastim may be preferred for:
  • Standard 3-week chemotherapy cycles 8
  • Patients with compliance concerns or difficulty with daily injections 8
  • Situations where convenience is prioritized 1

Cost Considerations

• The choice between filgrastim and pegfilgrastim should consider cost factors alongside clinical appropriateness 1
• Biosimilars of both filgrastim and pegfilgrastim are available and can be used interchangeably with their reference products 1

Special Populations

• In high-risk patients (>40% risk of febrile neutropenia), both pegfilgrastim and filgrastim show similar efficacy in preventing febrile neutropenia 1
• In moderate-risk patients (20-40% risk), pegfilgrastim may have an advantage over filgrastim in reducing febrile neutropenia rates 1