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      Systematic Review and Meta-analysis of Short- versus Long-Acting Granulocyte Colony-Stimulating Factors for Reduction of Chemotherapy-Induced Febrile Neutropenia

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          Abstract

          Introduction

          Short- and long-acting granulocyte-colony stimulating factors (G-CSFs) are approved for the reduction of febrile neutropenia. A systematic literature review was performed to identify randomized controlled trials (RCTs) and non-RCTs reporting the use of G-CSFs following chemotherapy treatment.

          Methods

          Medline ®/Medline in-process, Embase ®, and the Cochrane Library were searched for studies published between January 2003 and June 2016. A hand-search of relevant conference proceedings was conducted for meetings held between 2012 and 2016. Eligible studies were restricted to those reporting a direct, head-to-head comparison of short- versus long-acting G-CSFs for reduction of chemotherapy-induced febrile neutropenia. Risk-of-bias assessments were performed for full publications only.

          Results

          The search strategy yielded 4044 articles for electronic screening. Thirty-six publications were evaluated for the meta-analysis: 11 of 12 RCTs and 2 of 24 non-RCTs administered doses of the short-acting G-CSF filgrastim for ≥ 7 days. In RCT studies, there was no statistically significant difference in outcomes of interest between short- and long-acting G-CSFs. In non-RCTs, the overall risk was lower with long-acting G-CSF than with short-acting G-CSF for incidence of febrile neutropenia [overall relative risk (RR) = 0.67, P  = 0.023], hospitalizations (overall RR = 0.68, P  < 0.05), and chemotherapy dose delays (overall RR = 0.68, P  = 0.020).

          Conclusions

          Overall, the weight of evidence from RCTs indicates little difference in efficacy between the short- and long-acting G-CSFs if dosed according to recommended guidelines. There is some evidence for greater efficacy for long-acting G-CSFs in non-RCTs, which may be a result of under-dosing of short-acting G-CSFs in general practice in real-world usage.

          Funding

          Hospira Inc, which was acquired by Pfizer Inc in September 2015, and Pfizer Inc.

          Electronic supplementary material

          The online version of this article (10.1007/s12325-018-0798-6) contains supplementary material, which is available to authorized users.

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          Most cited references61

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          Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management.

          Cytotoxic chemotherapy suppresses the hematopoietic system, impairing host protective mechanisms and limiting the doses of chemotherapy that can be tolerated. Neutropenia, the most serious hematologic toxicity, is associated with the risk of life-threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcomes. The authors reviewed the recent literature to provide an update on research in chemotherapy-induced neutropenia and its complications and impact, and they discuss the implications of this work for improving the management of patients with cancer who are treated with myelosuppressive chemotherapy. Despite its importance as the primary dose-limiting toxicity of chemotherapy, much concerning neutropenia and its consequences and impact remains unknown. Recent surveys indicate that neutropenia remains a prevalent problem associated with substantial morbidity, mortality, and costs. Much research has sought to identify risk factors that may predispose patients to neutropenic complications, including febrile neutropenia, in an effort to predict better which patients are at risk and to use preventive strategies, such as prophylactic colony-stimulating factors, more cost-effectively. Neutropenic complications associated with myelosuppressive chemotherapy are a significant cause of morbidity and mortality, possibly compromised treatment outcomes, and excess healthcare costs. Research in quantifying the risk of neutropenic complications may make it possible in the near future to target patients at greater risk with appropriate preventive strategies, thereby maximizing the benefits and minimizing the costs. Copyright 2003 American Cancer Society.
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            Management of febrile neutropaenia: ESMO Clinical Practice Guidelines.

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              • Abstract: found
              • Article: not found

              A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy.

              We evaluated the efficacy of a single fixed 6 mg dose of pegfilgrastim (a pegylated version of filgrastim) per cycle of chemotherapy, compared with daily administration of filgrastim, in the provision of neutrophil support. Patients (n = 157) were randomized to receive either a single 6 mg subcutaneous (s.c.) injection of pegfilgrastim or daily 5 mg/kg s.c. injections of filgrastim, after doxorubicin and docetaxel chemotherapy (60 mg/m(2) and 75 mg/m(2), respectively). Duration of grade 4 neutropenia, depth of neutrophil nadir, incidence of febrile neutropenia, time to neutrophil recovery and safety information were recorded. A single 6 mg injection of pegfilgrastim was as effective as daily injections of filgrastim for all efficacy measures for all cycles. The mean duration of grade 4 neutropenia in cycle 1 was 1.8 and 1.6 days for the pegfilgrastim and filgrastim groups, respectively. Results for all efficacy end points in cycles 2-4 were consistent with the results from cycle 1. A trend towards a lower incidence of febrile neutropenia was noted across all cycles with pegfilgrastim compared with filgrastim (13% versus 20%, respectively). A single fixed dose of pegfilgrastim was as safe and well tolerated as standard daily filgrastim. A single fixed dose of pegfilgrastim administered once per cycle of chemotherapy was comparable to multiple daily injections of filgrastim in safely providing neutrophil support during myelosuppressive chemotherapy. Pegfilgrastim may have utility in other clinical settings of neutropenia.
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                Author and article information

                Contributors
                paul.cornes@yahoo.co.uk
                Journal
                Adv Ther
                Adv Ther
                Advances in Therapy
                Springer Healthcare (Cheshire )
                0741-238X
                1865-8652
                8 October 2018
                8 October 2018
                2018
                : 35
                : 11
                : 1816-1829
                Affiliations
                [1 ]Comparative Outcomes Group, 9 Royal Victoria Park, Bristol, BS10 6TD UK
                [2 ]ISNI 0000 0004 1937 0247, GRID grid.5841.8, Department of Hematology-Oncology, Hospital Clínic, , University of Barcelona, ; C/Casanova 143, 08036 Barcelona, Spain
                [3 ]ISNI 0000 0001 0440 1889, GRID grid.240404.6, Nottingham University Hospitals, ; Hucknall Road, Nottingham, NG5 1PB UK
                [4 ]ISNI 0000 0004 1936 9262, GRID grid.11835.3e, Sheffield University, Weston Park Hospital, ; Whitham Road, Sheffield, S10 2SJ UK
                [5 ]PharmaGenesis Oxford Central, Chamberlain House, 5 St Aldates Courtyard, Oxford, OX1 1BN UK
                [6 ]ISNI 0000 0000 9348 0090, GRID grid.418566.8, Pfizer Ltd, ; Ramsgate Road, Sandwich, CT13 9NJ UK
                [7 ]ISNI 0000 0000 8800 7493, GRID grid.410513.2, Pfizer Inc, ; 235 East 42nd Street, New York, NY 10017 USA
                Article
                798
                10.1007/s12325-018-0798-6
                6223993
                30298233
                12cee7e6-396d-4a3e-a163-fbe4db77d686
                © The Author(s) 2018, corrected publication October/2018
                History
                : 9 July 2018
                Funding
                Funded by: Pfizer
                Categories
                Review
                Custom metadata
                © Springer Healthcare Ltd., part of Springer Nature 2018

                chemotherapy,chemotherapy-induced febrile neutropenia,filgrastim,granulocyte colony-stimulating factor,neutropenia,oncology

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