Systematic Review and Meta-analysis of Short- versus Long-Acting Granulocyte Colony-Stimulating Factors for Reduction of Chemotherapy-Induced Febrile Neutropenia
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.
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.
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).
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.
Hospira Inc, which was acquired by Pfizer Inc in September 2015, and Pfizer Inc.
KeywordsChemotherapy Chemotherapy-induced febrile neutropenia Filgrastim Granulocyte colony-stimulating factor Neutropenia Oncology
This systematic literature review and meta-analysis was funded by Hospira Inc, which was acquired by Pfizer Inc. in September 2015, and by Pfizer Inc. Article processing charges were funded by Pfizer Inc.
Medical Writing, Editorial, and Other Assistance
This systematic literature review and meta-analysis was developed by Catherine R. Mitchell and Polly Field. Medical writing and editorial support was provided by Merry H. Saba, PharmD, and Elyse Smith, PhD, of Engage Scientific Solutions, and funded by Pfizer Inc.
All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Paul Cornes has received honoraria from Accord Healthcare, Amgen, Hospira/Pfizer Inc, Medicines for Europe/European Generics Medecines Association, Roche, Sandoz, and Teva Pharmaceutical Industries Ltd. Pere Gascon has provided consultancy/advisory services (uncompensated) for Hospira. Steve Chan and Khalid Hameed have nothing to disclose. Polly Field is Communications Director at PharmaGenesis Oxford Central, which received compensation from Hospira/Pfizer Inc for development of the systematic literature review and meta-analysis. Catherine R. Mitchell was a consultant for PharmaGenesis Oxford Central at the time of development of the systematic review and meta-analysis. Mark Latymer is a full-time employee of, and declares stock holdings and/or stock options from, Pfizer Inc. Luiz H. Arantes is a full-time employee of, and declares stock holdings and/or stock options from, Pfizer Inc.
Compliance with Ethics Guidelines
This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
All data generated or analyzed during this study are included in this published article/as supplementary information files.
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