Original Research

Outcomes in Patients With Curative Malignancies Receiving Filgrastim as Primary Prophylaxis

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Background: Granulocyte colony-stimulating factor (G-CSF) prophylaxis has been shown to reduce the risk and duration of chemotherapy-induced neutropenia and febrile neutropenia (FN) and is recommended for at-risk patients receiving chemotherapy. Within the South Texas Veterans Health Care System (STVHCS), daily filgrastim injections remain the preferred formulation of G-CSF for primary prophylaxis of FN.

Methods: This retrospective, single-center cohort study from September 2015 to September 2020 included 59 patients who received daily filgrastim as primary prophylaxis with a curative cancer diagnosis and a chemotherapy regimen. Patients had either a high risk for FN or a chemotherapy regimen with an intermediate risk for FN and additional risk factors. The primary outcome was the incidence of neutropenia/FN leading to treatment delays. Secondary outcomes included chemotherapy dose decreases or discontinuations, hospitalizations, days of hospitalization, infections, extended duration of filgrastim, and transitions to pegfilgrastim due to neutropenia/FN.

Results: Patients received a median (IQR) of 7 (5-10) doses of filgrastim for primary prophylaxis. Overall, 10 (17%) patients experienced treatment delays due to neutropenia/FN. Fifteen (25%) patients were hospitalized with a median (IQR) length of stay of 5 (4-7) days, 9 (15%) patients had documented infections, and 2 (3%) patients required a chemotherapy dose reduction. Additionally, 9 (15%) patients required an additional median (IQR) of 2 (2-5) doses of filgrastim, and 9 (15%) patients were transitioned to pegfilgrastim.

Conclusions: These results suggest that additional measures such as tracking postnadir absolute neutrophil counts should be performed to ensure patients receive an appropriate number of filgrastim doses to prevent complications associated with neutropenia/FN.


 

References

Febrile neutropenia (FN) frequently occurs in patients receiving chemotherapy, with the greatest risk of complications occurring in those who experience profound and prolonged neutropenia. Although granulocyte colony-stimulating factor (G-CSF) prophylaxis has been shown to reduce the risk and duration of chemotherapy-induced neutropenia and FN, there is no well-established optimal regimen.1 The 2022 National Comprehensive Cancer Network (NCCN) guidelines for hematopoietic growth factors recommend prophylaxis with G-CSF in at-risk patients receiving chemotherapy, specifically in chemotherapy regimens considered high risk for FN (incidence > 20%) or intermediate risk for FN (incidence 10% to 20%) with additional patient risk factors.2 The incidence of developing FN with at least 1 chemotherapy cycle is estimated at 10% to 50% of patients with solid tumors and > 80% of patients with hematologic malignancies.3 The rate of major complications (eg, hypotension, acute renal, respiratory, or heart failure) in the context of FN is 25% to 30%, and mortality is reported up to 11% in this population.4

Because of the significant consequences of neutropenia and FN, prevention is imperative due to the increase in morbidity and mortality, including chemotherapy delays, increased hospitalizations, chemotherapy dose reductions, and discontinuations that cause delays in care.5 In patients with curative malignancies, these consequences can negatively impact treatment efficacy and overall survival. Additionally, infections occur in 20% to 30% of patients with febrile episodes. Although fever is often the only clinical sign or symptom of infection, patients who are profoundly neutropenic may present with suspected infection and be afebrile or hypothermic.3

For filgrastim, the NCCN guidelines do not specify the total days of required injections, but state that a daily dose should be given until the postnadir absolute neutrophil count (ANC) recovers to normal or near normal levels by laboratory standards.2 It is uncommon in clinical practice to track postnadir ANCs due to frequent laboratory monitoring. Clinical trial data suggest an average duration of 11 days of daily filgrastim injections for ANC recovery; however, real-world data exist supporting a range from 4 to 10 days with a median of 7 injections per cycle for prevention of neutropenia or FN.6,7

At the South Texas Veterans Health Care System (STVHCS) in San Antonio, daily filgrastim injections are preferred due to cost; patients typically receive a 7-day course for primary prophylaxis for FN. In our study, we aimed to determine the outcomes in patients receiving daily filgrastim injections with a curative cancer diagnosis and a chemotherapy regimen with either high risk for FN, or a chemotherapy regimen with an intermediate risk for FN and additional patient risk factors. Before the initiation of data collection, this study was reviewed and determined to be exempt by the University of Texas Health Science Center at San Antonio Institutional Review Board.

Methods

STVHCS electronic health record reviews were performed to identify patients who received filgrastim primary prophylaxis (defined as filgrastim, tbo-filgrastim, or filgrastim-sndz) for a curative cancer diagnosis. Primary prophylaxis refers to the administration of G-CSF in the first cycle of chemotherapy before the onset of neutropenia. Patients received filgrastim prophylaxis if they were undergoing treatment with a chemotherapy regimen with either high risk for FN or a chemotherapy regimen with an intermediate risk for FN and additional patient risk factors. Risk factors for patients included prior chemotherapy or radiation therapy; persistent neutropenia; bone marrow involvement by tumor; recent surgery and/or open wounds; liver dysfunction (defined as total bilirubin > 2 mg/dL); renal dysfunction (defined as creatinine clearance < 50 mL/min); and those aged > 65 years receiving full chemotherapy dose intensity. Neutropenia is defined as a decrease in ANC < 1000 neutrophils/μL, whereas FN is defined as a single temperature of > 38.3 °C or > 38.0 °C for longer than 1 hour with < 500 neutrophils/μL or < 1000 neutrophils/μL predicted to decline to < 500 neutrophils/μL over the next 48 hours. All patients had their filgrastim dispensed for home administration during their chemotherapy appointment.

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