title: The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  The granulocyte colony-stimulating factor (G-CSF) is utilized to reduce neutropenic complications in patients receiving cancer chemotherapy. This study represents a systematic review and evidence summary of the impact of G-CSF support on chemotherapy dose intensity and overall mortality.
  
  
  METHODS
  All randomized controlled trials (RCTs) comparing chemotherapy with or without G-CSF support and reporting all-cause mortality with at least 2 years of follow-up were sought. Dual-blind data abstraction of disease, treatment, patient and outcome study results with conflict resolution by third party was carried out.
  
  
  RESULTS
  The search revealed 61 randomized comparisons of chemotherapy with or without initial G-CSF support. Death was reported in 4251 patients randomized to G-CSFs and in 5188 controls. Relative risk (RR) with G-CSF support for all-cause mortality was 0.93 (95% confidence interval: 0.90-0.96; P < 0.001). RR for mortality varied by intended chemotherapy dose and schedule: same dose and schedule (RR = 0.96; P = 0.060), dose dense (RR = 0.89; P < 0.001), dose escalation (RR = 0.92; P = 0.019) and drug substitution or addition (RR = 0.94; P = 0.003). Greater RR reduction was observed among studies with longer follow-up (P = 0.02), where treatment was for curative intent (RR = 0.91; P < 0.001), and where survival was the primary outcome (RR = 0.91; P < 0.001).
  
  
  CONCLUSIONS
  All-cause mortality is reduced in patients receiving chemotherapy with primary G-CSF support. The greatest impact was observed in RCTs in patients receiving dose-dense schedules.
authors.affiliation: Department of Medicine, Duke University, Durham. Electronic address: gary.lyman@duke.edu.
authors.forename: G H
authors.initials: GH
authors.lastname: Lyman
authors.affiliation: Department of Medicine, University of Washington, Seattle, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Dale
authors.affiliation: Department of Medicine, Duke University, Durham.
authors.forename: E
authors.initials: E
authors.lastname: Culakova
authors.affiliation: Department of Medicine, Duke University, Durham.
authors.forename: M S
authors.initials: MS
authors.lastname: Poniewierski
authors.affiliation: Department of Medicine, Duke University, Durham.
authors.forename: D A
authors.initials: DA
authors.lastname: Wolff
authors.affiliation: Department of Medicine, Duke University, Durham.
authors.forename: N M
authors.initials: NM
authors.lastname: Kuderer
authors.affiliation: Department of Medicine, Duke University, Durham.
authors.forename: M
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Medicine, Duke University, Durham.
authors.forename: J
authors.initials: J
authors.lastname: Crawford
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D005334:Fever / Q000188:drug therapy; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: granulocyte colony-stimulating factors; neutropenia; survival