title: Efficacy, effectiveness and safety of long-acting granulocyte colony-stimulating factors for prophylaxis of chemotherapy-induced neutropenia in patients with cancer: a systematic review.
abstract: OBJECTIVE
  Pegfilgrastim was introduced over a decade ago. Other long-acting granulocyte colony-stimulating factors (G-CSFs) have recently been developed. We systematically reviewed the efficacy, effectiveness and safety of neutropenia prophylaxis with long-acting G-CSFs in cancer patients receiving chemotherapy.
  
  
  METHODS
  We performed a systematic literature search of the MEDLINE, EMBASE and Cochrane Library databases, and abstracts from key congresses. Studies of long-acting G-CSFs for prophylaxis of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) were identified by two independent reviewers. Abstracts and full texts were assessed for final inclusion; risk of bias was evaluated using the Cochrane's tool. Effectiveness and safety results were extracted according to study type and G-CSF used.
  
  
  RESULTS
  Of the 839 articles identified, 41 articles representing different studies met the eligibility criteria. In five randomised controlled trials, 11 clinical trials and 17 observational studies across several tumour types and chemotherapy regimens, pegfilgrastim was used alone or compared with daily G-CSF, no G-CSF, no upfront pegfilgrastim or placebo. Studies generally reported lower incidence of CIN (4/7 studies), FN (11/14 studies), hospitalisations (9/13 studies), antibiotic use (6/7 studies) and adverse events (2/5 studies) with pegfilgrastim than filgrastim, no upfront pegfilgrastim or no G-CSF. Eight studies evaluated other long-acting G-CSFs; most (5/8) were compared to pegfilgrastim and involved patients with breast cancer receiving docetaxel-based therapy. Efficacy and safety profiles of balugrastim and lipegfilgrastim were comparable to pegfilgrastim in phase 3 studies. Efficacy and safety of other long-acting G-CSFs were mixed.
  
  
  CONCLUSIONS
  Pegfilgrastim reduced the incidence of FN and CIN compared with no prophylaxis. Most studies showed better efficacy and effectiveness for pegfilgrastim than filgrastim. Efficacy and safety profiles of lipegfilgrastim and balugrastim were similar to pegfilgrastim.
authors.affiliation: Institute of Pharmaceutical Medicine, University of Basel, Klingelbergstrasse 61, 4056, Basel, Switzerland, alena.pfeil@unibas.ch.
authors.forename: Alena M
authors.initials: AM
authors.lastname: Pfeil
authors.forename: Kim
authors.initials: K
authors.lastname: Allcott
authors.forename: Ruth
authors.initials: R
authors.lastname: Pettengell
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwenkglenks
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szabo
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000188:drug therapy* / Q000517:prevention & control*; D000077143:Docetaxel; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012709:Serum Albumin / Q000009:adverse effects / Q000627:therapeutic use*; D000075462:Serum Albumin, Human; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012709:Serum Albumin; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim; C000600093:balugrastim; D000075462:Serum Albumin, Human