Three Decades of G-CSF in Cancer Care: Reinforcing Evidence for Febrile Neutropenia Management and Prophylaxis

For over thirty years, granulocyte colony-stimulating factor (G-CSF) has played a pivotal role in the management of chemotherapy-induced neutropenia—a potentially fatal complication of anti-cancer treatment.¹ Recent clinical research, including a new 2025 prospective cohort study, reaffirms the benefits of G-CSF, particularly in reducing febrile neutropenia (FN), improving absolute neutrophil count (ANC) recovery, and minimizing infectious complications in patients undergoing myelosuppressive chemotherapy.²

Understanding G-CSF: A Cornerstone in Oncology Supportive Care

Cytotoxic anti-cancer regimen can result in chemotherapy-induced neutropenia (CIN) which affects more than 50% of cancer patients receiving the treatment. It markedly increases their susceptibility to infections, hospitalizations, and mortality.¹ G-CSF, a myeloid growth factor, stimulates the proliferation and differentiation of neutrophil precursors in the bone marrow, correcting neutropenia and accelerating immune recovery.^1,2

Since the first recombinant human G-CSF (filgrastim) received FDA approval in 1991, its clinical application has expanded. The drug significantly reduced the incidence and severity of neutropenia, FN, and associated infections. Later formulations like pegfilgrastim, with extended half-lives, allowed for once-per-cycle dosing, improving patient compliance.¹

 Real World Evidence from a 2025 Prospective Cohort Study

A recent single-center study conducted at Hayatabad Medical Complex in Pakistan evaluated the real-world efficacy of adjunctive G-CSF in adult cancer patients undergoing chemotherapy. The study measured clinical, hematological, and microbiological outcomes in 109 patients afflicted by various carcinomas - including breast, gastric, colon and lung cancers - over a one-year period.²

 Key Findings:

• Reduced Incidence of FN: None of the patients who received G-CSF developed FN, while 100% of those who did not receive G-CSF experienced FN.²
• Enhanced Neutrophil Recovery: G-CSF recipients demonstrated significantly faster ANC recovery, often within 5–7 days post-chemotherapy.²
• Lower Infection Rates: Bacterial infections were notably lower in the G-CSF group (8.22%) versus the non-G-CSF group (69.23%).²
• Improved Clinical Outcomes: No cases of fever were reported among G-CSF-treated patients, compared to 39.13% in the untreated group. The use of G-CSF also reduced the requirement for antibiotics and shortened hospital stays.²

These findings strongly support the clinical guidelines recommending G-CSF for high-risk FN chemotherapy protocols and older patients (age >50), who tend to have reduced bone marrow reserves and impaired immune function.²

 Aligning with Global Guidelines

The West Midlands Cancer Alliance (WMCA) and other international oncology bodies, such as ASCO and ESMO, provide comprehensive recommendations for G-CSF use. According to the WMCA's 2021 guidelines, G-CSF should be considered for:
• Primary prophylaxis in regimens with FN risk ≥20%.³
• Secondary prophylaxis after prior FN episodes.³
• Patients over 65, with comorbidities, or those receiving high-dose or intensive chemotherapy.³

Moreover, during the COVID-19 pandemic, expanded G-CSF use was endorsed to mitigate emergency care visits by preventing FN.³

Looking Ahead: Next-Generation G-CSFs

While short-acting filgrastim remains widely used, long-acting agents like pegfilgrastim have improved convenience. The development of third-generation G-CSFs, such as F-627 (Ryzneuta), offers promise for broader global access. F-627 is designed with Fc fusion technology for extended half-life and enhanced receptor activity, showing superior performance in preclinical and early-phase trials.¹

Conclusion: Strengthening the Case for Routine G-CSF Integration

The 2025 cohort study reinforces what decades of clinical use have already suggested: G-CSF remains an indispensable component of supportive oncology care. By reducing febrile neutropenia, promoting faster hematologic recovery, and lowering infection risk, G-CSF not only improves patient outcomes but also preserves chemotherapy intensity and reduces healthcare burdens.^1-3

As cancer care advances toward more personalized and intensive treatment regimens, integrating G-CSF—whether in its traditional or next-gen form—will be vital in ensuring safer, more effective therapy for patients worldwide.