title: Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: A systematic review.
abstract: BACKGROUND
  Febrile neutropenia (FN) is a serious side-effect of myelosuppressive chemotherapy. Several clinical trials and observational studies have evaluated the effects of prophylactic granulocyte colony-stimulating factors (G-CSFs) on risk of FN and related complications; however, no systematic reviews have focused on effectiveness in routine clinical practice. Here, we perform a systematic review assessing the comparative effectiveness of prophylaxis with a long-acting G-CSF (pegfilgrastim) versus short-acting G-CSFs (filgrastim, lenograstim, and filgrastim biosimilars) in cancer patients in real-world clinical settings.
  
  
  METHODS
  A systematic review was performed based on a pre-specified protocol and was consistent with the Cochrane Collaboration Handbook (2009) and the Centre for Reviews and Dissemination's Guidance for Undertaking Reviews in Health Care (2011). MEDLINE, Embase, BIOSIS, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library databases were searched for articles published from January 2002 to June 2014. Congress databases (MASCC/ASCO/ESMO) and Google Scholar were searched for abstracts published from January 2012 to August 2014. Filgrastim (NEUPOGEN®), lenograstim and nivestim (a filgrastim biosimilar) were the only short-acting G-CSFs and pegfilgrastim (Neulasta®) was the only long-acting G-CSF described in eligible studies. Outcomes of interest were FN, FN-related hospitalisation and other FN-related complications (death, chemotherapy dose delays and reductions, antimicrobial treatment, severe neutropenia and costs and resource use).
  
  
  RESULTS
  Of 1259 unique records identified, 18 real-world observational studies met predefined inclusion criteria; 15 were retrospective studies, and 3 were prospective studies. Multiple tumour types, chemotherapy regimens and geographical regions were included. Seven studies provided statistical comparisons of the risk of FN; risk of FN among patients receiving prophylaxis with pegfilgrastim versus short-acting G-CSF was significantly lower in three studies, numerically lower in three studies, and numerically higher in one study. Six studies provided statistical comparisons of the risk of FN-related hospitalisation; risk of FN-related hospitalisation among patients receiving prophylaxis with pegfilgrastim versus short-acting G-CSF was significantly lower in all six studies, though some variation was seen in subanalyses. Data for other outcomes were sparse with available results being generally consistent with the results seen for risk of FN and FN-related hospitalisation.
  
  
  CONCLUSIONS
  Based on the findings from this review of real-world comparative effectiveness studies, risks of FN and FN-related complications were generally lower for prophylaxis with pegfilgrastim versus prophylaxis with short-acting G-CSFs.
authors.affiliation: RTI Health Solutions, Manchester UK semitchell@rti.org.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mitchell
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.affiliation: RTI Health Solutions, Manchester UK BresMed Health Solutions, Sheffield, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Woods
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Garcia
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Kerri
authors.initials: K
authors.lastname: Hebard-Massey
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Rich
authors.initials: R
authors.lastname: Barron
authors.affiliation: RTI Health Solutions, Manchester UK NUS Yong Loo Lin School of Medicine, Singapore.
authors.forename: Miny
authors.initials: M
authors.lastname: Samuel
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000008:administration & dosage / Q000627:therapeutic use; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000188:drug therapy* / Q000517:prevention & control; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D000069585:Filgrastim / Q000008:administration & dosage / Q000627:therapeutic use*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D000078224:Lenograstim; D009369:Neoplasms / Q000188:drug therapy; D064887:Observational Studies as Topic; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D059451:Biosimilar Pharmaceuticals; D003692:Delayed-Action Preparations; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000078224:Lenograstim; D000069585:Filgrastim
keywords: Granulocyte colony-stimulating factor; febrile neutropenia; hospitalisation; real-world setting; systematic literature review