Colony-stimulating factors are prescribed to patients undergoing chemotherapy to reduce the risk of febrile neutropenia. Research suggests that 55% to 95% of colony-stimulating factor prescribing is inconsistent with national guidelines.
To examine whether a guideline-based standing order for primary prophylactic colony-stimulating factors improves use and reduces the incidence of febrile neutropenia.
This cluster randomized clinical trial, the Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER), involved 32 community oncology clinics in the US. Participants were adult patients with breast, colorectal, or non-small cell lung cancer initiating cancer therapy and enrolled between January 2016 and April 2020. Data analysis was performed from July to October 2021.
Sites were randomized 3:1 to implementation of a guideline-based primary prophylactic colony-stimulating factor standing order system or usual care. Automated orders were added for high-risk regimens, and an alert not to prescribe was included for low-risk regimens. Risk was based on National Comprehensive Cancer Network guidelines.
The primary outcome was to find an increase in colony-stimulating factor use among high-risk patients from 40% to 75%, a reduction in use among low-risk patients from 17% to 7%, and a 50% reduction in febrile neutropenia rates in the intervention group. Mixed model logistic regression adjusted for correlation of outcomes within a clinic.
A total of 2946 patients (median [IQR] age, 59.0 [50.0-67.0] years; 2233 women [77.0%]; 2292 White [79.1%]) were enrolled; 2287 were randomized to the intervention, and 659 were randomized to usual care. Colony-stimulating factor use for patients receiving high-risk regimens was high and not significantly different between groups (847 of 950 patients [89.2%] in the intervention group vs 296 of 309 patients [95.8%] in the usual care group). Among high-risk patients, febrile neutropenia rates for the intervention (58 of 947 patients [6.1%]) and usual care (13 of 308 patients [4.2%]) groups were not significantly different. The febrile neutropenia rate for patients receiving high-risk regimens not receiving colony-stimulating factors was 14.9% (17 of 114 patients). Among the 585 patients receiving low-risk regimens, colony-stimulating factor use was low and did not differ between groups (29 of 457 patients [6.3%] in the intervention group vs 7 of 128 patients [5.5%] in the usual care group). Febrile neutropenia rates did not differ between usual care (1 of 127 patients [0.8%]) and the intervention (7 of 452 patients [1.5%]) groups.
In this cluster randomized clinical trial, implementation of a guideline-informed standing order did not affect colony-stimulating factor use or febrile neutropenia rates in high-risk and low-risk patients. Overall, use was generally appropriate for the level of risk. Standing order interventions do not appear to be necessary or effective in the setting of prophylactic colony-stimulating factor prescribing.
ClinicalTrials.gov Identifier: NCT02728596.

UNASSIGNED: Approximately 60,000 patients are hospitalised annually due to chemotherapy-induced febrile neutropenia (FN) in the United States alone. Febrile neutropenia is primarily managed by antibiotics and granulocyte-colony-stimulating factors (G-CSFs). However, there are inconsistent recommendations regarding dose, frequency, and duration for G-CSF therapy. We conducted this study to assess the use of G-CSFs in a community-based teaching hospital in compliance with the National Comprehensive Cancer Network (NCCN) guidelines.
UNASSIGNED: We retrospectively reviewed medical records of adult patients diagnosed with non-myeloid malignancies who received filgrastim in a community-based teaching hospital from November 2014 to April 2015.
UNASSIGNED: Of 90 patients, 77% received filgrastim for FN treatment, 19% for primary prophylaxis, and 4% for secondary prophylaxis. The dose of filgrastim was appropriate in 93% of patients, while 7% received a sub-optimal dose without the worsening of their clinical outcomes. We could not assess the duration of therapy for 38 patients who either died or were discharged before achieving the desired absolute neutrophil count (ANC). Of the 69 patients treated for FN, only 33% received filgrastim until they achieved the ANC goal (1,500-8,000/μL), while 36% continued to receive filgrastim treatment beyond the desired ANC goal.
UNASSIGNED: In our study, filgrastim was correctly prescribed; however, the ANC goal was not achieved in 47% of the patients. If the recommended ANC range had been targeted, a minimum of 28 doses could have been potentially avoided. This approach would have saved approximately $56,000. Therefore, future protocols should focus on pharmacist-led interventions to optimise G-CSF usage.

Neutropenia induced by chemotherapy (CT) is an infection risk factor associated to greater morbidity/mortality and dose-limiting toxicity that on many occasions requires a reduction of the dose of cytostatics or a delay in the administration of treatment. This may have a negative effect on the patient\'s quality of life and even diminish the efficacy of the treatment, especially when the intention is to cure or prolong survival. Management of treatment or prophylaxis of grade 3-4 neutropenia and febrile neutropenia with myeloid growth factors (CSF) varies very much in clinical practice, both in the time of starting treatment and the types of patients it is given to. The need to generalise and facilitate practice based on clinical evidence has led the Spanish Society of Medical Oncology (SEOM) to prepare clinical practice guidelines on the use of myeloid growth factors.

Chemotherapy-induced neutropenia and its complications are major dose-limiting toxicities of cancer chemotherapy. The myeloid growth factors have been shown to reduce the risk of neutropenic events across malignancies, regimens, and associated risk categories often enabling the delivery of greater chemotherapy dose intensity. Three different practice guidelines for the myeloid growth factors have recently been published by major professional organizations. A comprehensive review and comparison of the guidelines using a priori structured content criteria and a previously validated quality appraisal tool are reported. Consistency in the final recommendations from these guidelines is observed for primary prophylaxis with the colony-stimulating factors (CSFs) when the risk of febrile neutropenia is in the range of 20% or greater. There is also consistency in the recommendation that patients receiving regimens associated with lower risk should have CSF use guided by individual risk assessment. Critical quality appraisal indicates that the scope and purpose, stakeholder involvement, and applicability of the guidelines differ little. There is more emphasis on comprehensive literature reviews in the ASCO and EORTC guidelines while the NCCN guidelines are more current based on systematic annual updates. The clarity of presentation also favors the NCCN guidelines with recommendations generally presented as both text and algorithmic diagram. All three new or updated guidelines recommend prophylactic use of the myeloid growth factors in patients at greater than a 20% risk of febrile neutropenia and in those with important factors increasing individual risk of neutropenic complications.

OBJECTIVE: Clinical practice guidelines for the prevention of febrile neutropenia in patients receiving cancer chemotherapy utilizing the myeloid growth factors have been developed by several major international professional organizations. This review provides updates on the current status of these guidelines and summarizes recent reported studies currently under review by guideline panels which may alter guideline recommendations.
RESULTS: Whereas the consensus guidelines from the National Comprehensive Cancer Network (NCCN) are updated annually, previous evidence-based recommendations from the American Society of Clinical Oncology (ASCO) and the European Organisation for Research and Treatment of Cancer (EORTC) are currently undergoing an update in their evidence base and recommendations. These updates will consider and base new recommendations on recent important studies related to the efficacy, safety, and cost of these agents in the prevention of neutropenic complications including febrile neutropenia. New information relating to the risk of second malignancies and the ability of the myeloid growth factors to sustain or increase chemotherapy dose intensity and improve overall survival is reviewed.
CONCLUSIONS: Current guideline recommendations for the prevention of febrile neutropenia are reviewed along with recent published results likely to alter future guideline recommendations on the use of these agents.

Neutropenia is a common complication of cancer chemotherapy. Colony-stimulating factors (CSF) may be used to avoid neutropenia-associated complications. The Spanish Society of Medical Oncology (SEOM) recently constituted a working group to review the main issues concerning the use of CSF and carried out a consensus process about the use of CSF in cancer patients, held in Madrid on 26 May 2006. The group concluded the following recommendations: prophylactic use of CSF is recommended when a rate of febrile neutropenia (FN) higher than 20% is expected without the use of CSF or when additional risk factors for neutropenia exist; therapeutic use of CSF is recommended in order to treat FN episodes but not to treat afebrile neutropenic episodes. In addition, the use of CSF is considered effective when used to mobilise stem cells before high-dose chemotherapy and when used for chemotherapy schedule optimisation in dose-dense and in dose-intense regimens.

Chemotherapy-induced neutropenia (CIN) is a common and serious toxicity of cancer chemotherapy. It can lead to febrile neutropenia (FN), which often requires patients to be hospitalised for intravenous antibiotic therapy. Chemotherapy dose reductions or delays, which can compromise clinical outcomes, may also result from CIN and FN. Prophylactic use of colony-stimulating factors (CSFs) reduces the incidence, duration, and severity of FN, and there is evidence that it helps maintain scheduled chemotherapy dose delivery. In 2006, three organisations published new or updated guidelines for the use of CSFs in cancer treatment. Each recommends that FN risk be determined individually for each patient, taking into account patient- and disease-specific risk factors, the chemotherapy regimen, and treatment intent. Particular consideration should be given to patients who are > or =65 years old, receiving chemotherapy regimens associated with > or =20% risk of FN, receiving dose-dense chemotherapy, and receiving treatment that is adjuvant, potentially curative, or intended to prolong survival. Accordingly, oncology nurses can play an important role in assessing and identifying patients at risk for FN before every chemotherapy cycle. There is evidence that, regardless of practice type or size, implementing guidelines for CSF use within a multidisciplinary team improves patient outcomes.

Chemotherapy-associated neutropenia is often dose-limiting and may compromise treatment efficacy. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF) are increasingly used to prevent febrile neutropenia (FN) or to increase dose-density. This review discusses recent changes in treatment guidelines for chemotherapy-associated neutropenia. Primary prophylactic use of CSFs is now recommended as a treatment option at an overall risk of FN of 20%, not taking into account cost-effectiveness. To estimate the risk of FN, patient-, disease-, and treatment-related factors predicting an adverse outcome of FN have been determined. Dose-dense chemotherapy has become feasible with the use of CSFs. However, clinical benefit has been shown only for specific chemotherapy regimens in breast cancer, small cell lung cancer (SCLC), and non-Hodgkin\'s lymphoma (NHL), for the latter particularly for patients above 60 years of age. Strategies are being developed to tailor the use of CSFs to patients with a high risk of adverse outcome of FN.

OBJECTIVE: To review and determine the applicability of the 2006 National Comprehensive Cancer Network (NCCN) clinical practice guidelines for the use of myeloid growth factors in adult patients treated with chemotherapy for solid tumors and nonmyeloid malignancies.
METHODS: Published guidelines, original research, review articles, and conference presentations.
RESULTS: Chemotherapy-induced neutropenia is a common adverse effect of myelosuppressive chemotherapy that may lead to life-threatening infections, prolonged hospitalization, increased IV antibiotic use, and dose reductions or delays that affect patients\' quality of life and clinical outcomes.
CONCLUSIONS: Before treatment begins, nurses should determine which patients are at greater risk for chemotherapy-induced neutropenia and implement an appropriate plan of care.
CONCLUSIONS: Nurses are in an ideal position to implement a risk assessment tool and play an integral role in directing the quality of patient care. Implementing the NCCN guidelines is one way to facilitate standardization of care.

Grade 3 and 4 neutropenia as well as febrile neutropenia have been demonstrated to occur in all tumor types and are clearly associated with major morbidity and significant mortality; this is particularly true when myelosuppressive regimens are used with curative intent as is the case in most breast cancer and non-Hodgkin\'s lymphoma regimens. Myeloid colony-stimulating factors (CSFs) substantially decrease the risk of severe and febrile neutropenia. Although the white cell growth factors might not be cost-effective at lower risks of febrile neutropenia, they clearly benefit other outcomes such as the incidence of severe neutropenia and febrile neutropenia, hospitalization, and mortality. Updated guidelines from the American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the European Organisation for Research and Treatment of Cancer now recommend primary prophylaxis or first-cycle use of white cell growth factors with regimens where the occurrence of febrile neutropenia is approximately 20% (as well as when other risk factors are present). This article briefly describes the rationale for the development of several of the guideline changes as well as highlights some of the ongoing issues related to the use of CSFs.