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      SEOM clinical practice guideline: management and prevention of febrile neutropenia in adults with solid tumors (2018)

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          Abstract

          Febrile neutropenia (FN) is a common dose-limiting toxicity of chemotherapy, with a profound impact on the evolution of patients with cancer, due to the potential development of serious complications, mortality, delays, and decrease in treatment intensity. This article seeks to present an updated clinical guideline, with recommendations regarding the diagnosis, prevention, and treatment of febrile neutropenia in adults with solid tumors. The aspects covered include how to properly approach the risk of microbial resistances, epidemiological aspects, considerations about the initial empirical approach adapted to the risk, special situations, and prevention of complications. A decision-making algorithm is included for use in the emergency department based on a new, validated tool, the Clinical Index of Stable Febrile Neutropenia, which can be used in patients with solid tumors who appear stable in the initial phase of neutropenic infections, and can help detect those at high risk for complications in whom early discharge must be avoided.

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          Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients.

          Nicole M Kuderer, David C. Dale, Jeffrey Crawford … (2006)
          Hospitalization for febrile neutropenia (FN) in cancer patients is associated with considerable morbidity, mortality, and cost. The study was undertaken to better define mortality, length of stay (LOS), cost, and risk factors associated with mortality and prolonged hospitalization in cancer patients with FN. The longitudinal discharge database derived from 115 US medical centers was used to study all adult cancer patients hospitalized with FN between 1995 and 2000, comprising a total of 41,779 patients. Primary outcomes included mortality, LOS, and cost per episode. Overall, in-hospital mortality was 9.5%. Patients without any major comorbidities had a 2.6% risk of mortality, whereas 1 major comorbidity was associated with a 10.3% and more than 1 major comorbidity with a > or = 21.4% risk of mortality, respectively. Mean (median) length of stay was 11.5 (6) days, and the mean (median) cost was $19,110 ($8,376) per episode of FN. Patients hospitalized for > or = 10 days (35% of all patients) accounted for 78% of overall cost. Independent major risk factors for inpatient mortality included invasive fungal infections, Gram-negative sepsis, pneumonia and other lung disease, cerebrovascular, renal, and liver disease. Main predictors for LOS > or = 10 days included leukemia, invasive fungal infections, other types of infection, and several comorbid conditions. Factors associated with increased mortality, LOS, and cost in hospitalized adult cancer patients with FN include patient characteristics, type of malignancy, comorbidities, and infectious complications. These factors may be useful in identifying patients at increased risk of serious medical complications and mortality for more aggressive supportive care measures. Copyright 2006 American Cancer Society
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            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.

            M S Aapro, J Bohlius, D A Cameron … (2011)
            Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (≥65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (≥20%) or intermediate (10-20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10-20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated. Filgrastim biosimilars are also approved for use in Europe. While other forms of G-CSF, including biosimilars, are administered by a course of daily injections, pegfilgrastim allows once-per-cycle administration. Choice of formulation remains a matter for individual clinical judgement. Evidence from multiple low level studies derived from audit data and clinical practice suggests that some patients receive suboptimal daily G-CSFs; the use of pegfilgrastim may avoid this problem. Copyright © 2010 Elsevier Ltd. All rights reserved.
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              2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline.

              Thomas Smith, James Khatcheressian, Gary H Lyman … (2006)
              To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF). The Update Committee completed a review and analysis of pertinent data published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness. The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia (FN) is an important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of FN is approximately 20% and no other equally effective regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose-intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF.
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                Author and article information

                Contributors
                A. Carmona-Bayonas: alberto.carmonabayonas@gmail.com
                P. Jimenez-Fonseca: palucaji@hotmail.com
                E. M. de Castro: evamdecastro@hotmail.com
                E. Mata: elenamata28@hotmail.com
                M. Biosca: mbiosca@vhebron.net
                A. Custodio: anabcustodio@gmail.com
                J. Espinosa: javiere@sescam.jccm.es
                E. G. Vázquez: elisagarciavazquez@gmail.com
                F. Henao: ferheca@gmail.com
                F. Ayala de la Peña:
                ORCID: http://orcid.org/0000-0001-6311-920X
                frayala@um.es
                Journal
                Journal ID (nlm-ta): Clin Transl Oncol
                Journal ID (iso-abbrev): Clin Transl Oncol
                Title: Clinical & Translational Oncology
                Publisher: Springer International Publishing (Cham )
                ISSN (Print): 1699-048X
                ISSN (Electronic): 1699-3055
                Publication date (Electronic): 23 November 2018
                Publication date PMC-release: 23 November 2018
                Publication date (Print): 2019
                Volume: 21
                Issue: 1
                Pages: 75-86
                Affiliations
                [1 ]ISNI 0000 0004 1765 5898, GRID grid.411101.4, Hematology and Medical Oncology Department, , Hospital Universitario Morales Meseguer, IMIB, ; Avenida Marqués de los Vélez, 30008 Murcia, Spain
                [2 ]ISNI 0000 0001 2176 9028, GRID grid.411052.3, Medical Oncology Department, , Hospital Universitario Central de Asturias, ; Oviedo, Spain
                [3 ]ISNI 0000 0001 0627 4262, GRID grid.411325.0, Medical Oncology Department, , Hospital Universitario Marqués de Valdecilla, ; Santander, Spain
                [4 ]GRID grid.497559.3, Medical Oncology Department, , Complejo Hospitalario de Navarra, ; Pamplona, Spain
                [5 ]ISNI 0000 0001 0675 8654, GRID grid.411083.f, Medical Oncology Department, , Hospital Vall D’Hebron, ; Barcelona, Spain
                [6 ]ISNI 0000 0000 8970 9163, GRID grid.81821.32, Medical Oncology Department, , Hospital Universitario La Paz, ; Madrid, Spain
                [7 ]CIBERONC (CB16/12/00398), Madrid, Spain
                [8 ]GRID grid.411096.b, Medical Oncology Department, , Hospital General de Ciudad Real, ; Ciudad Real, Spain
                [9 ]ISNI 0000 0001 0534 3000, GRID grid.411372.2, Infectious Disease Department, , Hospital Universitario Virgen de la Arrixaca, ; Murcia, Spain
                [10 ]ISNI 0000 0001 2287 8496, GRID grid.10586.3a, Departamento de Medicina, Facultad de Medicina, , Universidad de Murcia, ; Murcia, Spain
                [11 ]Medical Oncology Department, Complejo Hospitalario Regional Virgen Macarena, Seville, Spain
                Author information
                http://orcid.org/0000-0001-6311-920X
                Article
                Publisher ID: 1983
                DOI: 10.1007/s12094-018-1983-4
                PMC ID: 6339667
                PubMed ID: 30470991
                SO-VID: 46dea18b-3ed7-4343-8f72-70826caac266
                Copyright © © The Author(s) 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Date received : 6 November 2018
                Date accepted : 8 November 2018
                Categories
                Subject: Clinical Guides in Oncology
                Custom metadata
                issue-copyright-statement © Federación de Sociedades Españolas de Oncología (FESEO) 2019

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cisne score,febrile neutropenia,seom,clinical practice guideline
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: cisne score, febrile neutropenia, seom, clinical practice guideline

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