Prophylactic Use of Filgrastim on Days 7, 11 and 14 in Patients Receiving R-CHOP for Non-Hodgkin's Lymphoma
Authors: El- Shakankery Sherief , Gabriel Sumantha , Groves Emma 
Published: November 2019

Introduction
Chemotherapy-induced febrile neutropenia (FN) is a side effect of cytotoxic chemotherapy and a major risk factor for infection as well as a dose-limiting toxicity. One method of reducing the incidence of febrile neutropenia is through the use of granulocyte stimulating factor (G-CSF).
Patients with Non-Hodgkin's Lymphoma (NHL) receiving R- CHOP chemotherapy are thought to have a 10-20% risk of FN (Aapro et al 2010). Elderly patients (aged 65 and over) have an elevated risk of FN. The Newcastle upon Tyne Hospitals (NuTH) local guidelines recommend a novel regime prescribing one dose of filgrastim on days 7, 11 and 14 of treatment regime as primary prophylaxis.
Several randomised studies and retrospective reviews of practice have examined the question of G-CSF prophylaxis in older patients. There is little doubt that the use of G-CSF as primary prophylaxis in this group reduces the incidence of FN, however the data are conflicting with respect to impact on overall survival (Osby et al 2003. Doorduijn et al 2003)
Aims
To audit prophylactic G-CSF prescribing against trust guidelines for patients over 65 with NHL receiving R-CHOP chemotherapy. We also assessed the frequency of hospital admissions for FN in patients over 65 receiving curative R-CHOP for NHL.
Methods
Patients with NHL over 65 who received R-CHOP at NuTH between 01/06/2017 - 31/01/2018 were identified using our electronic chemotherapy prescribing system. Electronic medical records were used to extract patient, chemotherapy, and hospital admission details. A data collection tool was used to record; patient age, cycle number, details about neutropenic sepsis related admissions and neutrophil counts between 1- 4 days prior to a cycle commencing.
Results
30 patients with an average age of 73, cumulatively received 138 cycles of R-CHOP during the defined time period. 91.3% (126/138) of G-CSF prescriptions co-prescribed with chemotherapy were in accordance with trust policy. G-CSF on day 7, 11 and 14 corresponded with 8 hospital neutropenic admissions and 0 non-neutropenic. Comparatively 8.7% (12/138) of G-CSF prescriptions were for ≥5 days and corresponded with 5 hospital admissions with FN and 1 non-neutropenic. However, patients who received 5 or more days G-CSF had multiple risk factors for FN or had a previous episode of FN. The average length of admission due to FN was 6 days which has an associated financial implication. 17 chemotherapy prescriptions were dose reduced, of which 82.4% (14/17) were co-prescribed with the day 7, 11 and 14 regime. There were no deaths as a result of neutropenic sepsis in this cohort of 30 patients.
Conclusion
The NuTH G-CSF regime resulted in FN admission at a rate of 6.35% (8/126). This is lower than the expected rate of 10-20 % in the absence of G-CSF prophylaxis. These data support the use of the modified regimen of filgrastim on days 7, 11 and 14.
References
Aapro, M.S. et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. European Journal of Cancer, Volume 47, Issue 1, 8 - 32
Doorduijn JK, an der Holt B, Imhoff GW, Hem KG, Kramer MHH, Oers MHJ, et al. CHOP compared to CHOP plus granulocyte colony‐stimulating factor in elderly patients with aggressive Non‐Hodgkin's Lymphoma. Journal of Clinical Oncology 2003;21(16):3041‐50.
Ösby K, Hagberg H, Kvaloy S, Teerenhovi L, Anderson H, Cavallin‐Stahl E, et al. CHOP is superior to CNOP in elderly patients with aggressive lymphoma while outcome is unaffected by filgrastim treatment: results of a Nordic Lymphoma Group randomized trial. Blood 2003;101(10):3840‐8.

Disclosures
Gabriel: Abbvie: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Kite: Honoraria.

OffLabel Disclosure:
Filgrastim - granulocyte colony stimulating factor