title: Colony-stimulating factors for chemotherapy-induced febrile neutropenia.
abstract: BACKGROUND
  Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting.
  
  
  OBJECTIVE
  To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer.
  
  
  METHODS
  We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles.
  
  
  METHODS
  We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children.
  
  
  METHODS
  We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software.
  
  
  RESULTS
  Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897 participants; low quality evidence). Individuals who received CSF plus antibiotics were less likely to be hospitalized for more than 10 days (risk ratio (RR) 0.65 (95% CI 0.44 to 0.95) P = 0.03; 8 RCTs; 1221 participants; low quality evidence) and had more number of participants with a more faster neutrophil recovery (RR 0.52 (95% CI 0.34 to 0.81) P = 0.004; 5 RCTs; 794 participants; moderate quality evidence) than those treated with antibiotics alone. Similarly, participants receiving CSF plus antibiotics had shorter duration of neutropenia (standardized mean difference (SMD) -1.70 (95% CI -2.65 to -0.76) P = 0.0004; 9 RCTs; 1135 participants; moderate quality evidence), faster recovery from fever (SMD -0.49 (95% CI -0.90 to -0.09) P value = 0.02; 9 RCTs; 966 participants; moderate quality evidence) and shorter duration of antibiotics use (SMD -1.50 (95% CI -2.83 to -0.18) P = 0.03; 3 RCTs; 457 participants; low quality evidence) compared with participants receiving antibiotics alone. We found no significant difference in the incidence of deep venous thromboembolism (RR 1.68 (95% CI 0.72 to 3.93) P = 0.23; 4 RCTs; 389 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. We found higher incidence of bone or joint pain or flu-like symptoms (RR 1.59 (95% CI 1.04 to 2.42) P = 0.03; 6 RCTs; 622 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. Overall, the methodological quality of studies was moderate to low across different outcomes. The main reasons to downgrade the quality of evidence were inconsistency across the included studies and imprecision of results.
  
  
  CONCLUSIONS
  The use of a CSF plus antibiotics in individuals with chemotherapy-induced febrile neutropenia had no effect on overall mortality, but reduced the amount of time participants spent in hospital and improved their ability to achieve neutrophil recovery. It was not clear whether CSF plus antibiotics had an effect on infection-related mortality. Participants receiving CSFs had shorter duration of neutropenia, faster recovery from fever and shorter duration of antibiotics use.
authors.affiliation: Center for Evidence Based Medicine and Health Outcomes Research, University of South Florida, Tampa, Florida, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Mhaskar
authors.forename: Otavio Augusto Camara
authors.initials: OA
authors.lastname: Clark
authors.forename: Gary
authors.initials: G
authors.lastname: Lyman
authors.forename: Tobias
authors.initials: T
authors.lastname: Engel Ayer Botrel
authors.forename: Luciano
authors.initials: L
authors.lastname: Morganti Paladini
authors.forename: Benjamin
authors.initials: B
authors.lastname: Djulbegovic
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000188:drug therapy*; D002648:Child; D003115:Colony-Stimulating Factors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic
chemical_list: D000900:Anti-Bacterial Agents; D003115:Colony-Stimulating Factors; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor