What is the recommended use and dosage of Tbo-filgrastim (granulocyte-colony stimulating factor, G-CSF) for patients at high risk of febrile neutropenia due to chemotherapy?

Tbo-filgrastim for Patients at High Risk of Febrile Neutropenia

Tbo-filgrastim should be administered at a dose of 5 mcg/kg subcutaneously once daily, starting 1-3 days after completion of chemotherapy and continuing until post-nadir absolute neutrophil count (ANC) recovery to normal or near-normal levels. 1, 2

Indications and Risk Assessment

Tbo-filgrastim is indicated for patients at high risk of febrile neutropenia (FN) due to chemotherapy. High-risk patients include:

• Those receiving chemotherapy regimens with ≥20% risk of FN
• Patients who experienced FN in a previous chemotherapy cycle
• Patients with dose-limiting neutropenic events in previous cycles
• Patients receiving curative or adjuvant treatment where maintaining dose intensity is critical

Risk Stratification Algorithm:

1. High risk (>20% risk of FN): Prophylactic tbo-filgrastim recommended
2. Intermediate risk (10-20% risk of FN): Consider tbo-filgrastim based on additional risk factors:
   • Age >65 years
   • Advanced disease stage
   • Previous chemotherapy or radiation
   • Poor performance status
   • Pre-existing neutropenia
   • Open wounds or active infections
3. Low risk (<10% risk of FN): Routine use not recommended unless significant risk for serious consequences

Dosing and Administration

• Dose: 5 mcg/kg subcutaneously once daily 1
• Timing: Start 1-3 days after completion of chemotherapy 1, 2
• Duration: Continue until ANC recovery to normal or near-normal levels by laboratory standards 1
• Route: Subcutaneous administration is preferred 1

Clinical Evidence and Efficacy

Tbo-filgrastim has demonstrated efficacy comparable to filgrastim in clinical trials. The FDA approval was based on three randomized clinical trials involving 680 cancer patients, showing:

• Equivalent efficacy to filgrastim in reducing the duration of severe neutropenia
• Superior to placebo in reducing the duration of severe neutropenia and incidence of FN
• Similar toxicity profile to filgrastim 1

A pivotal Phase 3 study in 348 chemotherapy-naive patients with breast cancer showed tbo-filgrastim significantly reduced the duration of severe neutropenia compared to placebo (1.1 days vs. 3.8 days, p<0.0001) 2.

Monitoring and Follow-up

• Evaluate patients before each subsequent chemotherapy cycle to reassess risk
• If FN or dose-limiting neutropenia occurs despite tbo-filgrastim use, consider chemotherapy dose reduction or change in regimen 1
• Monitor for potential adverse effects:
  • Bone pain (most common adverse reaction)
  • Splenic rupture
  • Acute respiratory distress syndrome
  • Allergic reactions
  • Sickle cell crisis in patients with sickle cell disorders

Important Precautions

• Do not administer within 24 hours before or after cytotoxic chemotherapy 3
• Do not use concurrently with radiation therapy 1
• Avoid use in patients with known hypersensitivity to E. coli-derived proteins
• Use with caution in patients with pre-existing autoimmune disorders
• Monitor closely for potential development of leukocytosis (WBC counts >100,000 x 10^6/L) 2

Comparison with Other G-CSFs

While tbo-filgrastim requires daily administration, pegfilgrastim offers the convenience of a single 6 mg injection per chemotherapy cycle. Consider pegfilgrastim for patients who cannot return for daily injections due to distance or mobility issues 1, 4.

Meta-analyses have shown that pegfilgrastim may be associated with a lower incidence of FN compared to filgrastim (RR = 0.64; 95% CI, 0.43-0.97) 4, but tbo-filgrastim remains an effective option when daily monitoring and dose adjustment are preferred.