title: Interpreting febrile neutropenia rates from randomized, controlled trials for consideration of primary prophylaxis in the real world: a systematic review and meta-analysis.
abstract: BACKGROUND
  Guidelines recommend primary prophylaxis (PP) with granulocyte-colony-stimulating factors (G-CSF) for patients above a febrile neutropenia (FN) risk threshold of 20%. Practitioners often use FN rates of regimens based on data from randomized, controlled trials (RCTs), which are often comprised of highly selected patients. Patients in the community setting may be at higher risk of FN.
  
  
  METHODS
  A systematic literature search was conducted for full-length articles reporting FN rates for breast cancer-related chemotherapies between January 1996 and February 2014. A regimen was included if there was at least one RCT and one observational study. Meta-regression was used to model the odds of FN.
  
  
  RESULTS
  130 studies involving 29 regimens and 50 069 patients were identified. Sixty-five observational study (n = 7812) and 110 RCT (n = 42 257) cohorts were included. The unadjusted FN rate was 11.7% in observational and 7.9% in RCT cohorts. The univariable odds ratio (OR) for FN in the observational study compared with RCT cohorts was 1.58 [95% confidence interval (CI) 1.09-2.28; P = 0.017]. The FN rates remained significantly higher in the observational study compared with RCT cohorts (OR = 1.74; 95% CI 1.15-2.62; P = 0.012) after adjusting for age, chemotherapy intent, and regimen; this meant that a 13% (95% CI 8.7% to 17.9%) FN rate in RCT would translate into 20% FN rate in observational study.
  
  
  CONCLUSIONS
  FN rates in the observational studies are significantly higher than suggested by RCTs. Guidelines should clarify how FN rates from RCTs should be applied in clinical practice. Large population-based studies are needed to confirm FN rates in the real world.
authors.affiliation: Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto.
authors.forename: J
authors.initials: J
authors.lastname: Truong
authors.affiliation: Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto.
authors.forename: E K
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto Department of Medicine, University of Toronto, Toronto.
authors.forename: M E
authors.initials: ME
authors.lastname: Trudeau
authors.affiliation: Department of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto Department of Medicine, University of Toronto, Toronto Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto Canadian Centre for Applied Research in Cancer Control, Canada kelvin.chan@sunnybrook.ca.
authors.forename: K K W
authors.initials: KK
authors.lastname: Chan
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D064147:Febrile Neutropenia / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: cancer; chemotherapy; febrile neutropenia; granulocyte-colony-stimulating factors; risk factor