title: Erythropoietin or darbepoetin for patients with cancer.
abstract: BACKGROUND
  Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoiesis stimulating agents (ESAs) and red blood cell transfusions.
  
  
  OBJECTIVE
  To assess the effects of ESAs to either prevent or treat anaemia in cancer patients.
  
  
  METHODS
  This is an update of a Cochrane review first published in 2004. We searched the Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE and other databases. Searches were done for the periods 01/1985 to 12/2001 for the first review, 1/2002 to 04/2005 for the first update and to November 2011 for the current update. We also contacted experts in the field and pharmaceutical companies.
  
  
  METHODS
  Randomised controlled trials on managing anaemia in cancer patients receiving or not receiving anti-cancer therapy that compared the use of ESAs (plus transfusion if needed).
  
  
  METHODS
  Several review authors assessed trial quality and extracted data. One review author assessed quality assessment and extracted data, a second review author checked for correctness.
  
  
  RESULTS
  This update of the systematic review includes a total of 91 trials with 20,102 participants. Use of ESAs significantly reduced the relative risk of red blood cell transfusions (risk ratio (RR) 0.65; 95% confidence interval (CI) 0.62 to 0.68, 70 trials, N = 16,093). On average, participants in the ESAs group received one unit of blood less than the control group (mean difference (MD) -0.98; 95% CI -1.17 to -0.78, 19 trials, N = 4,715). Haematological response was observed more often in participants receiving ESAs (RR 3.93; 95% CI 3.10 to 3.71, 31 trials, N = 6,413). There was suggestive evidence that ESAs may improve Quality of Life (QoL). There was strong evidence that ESAs increase mortality during active study period (hazard ratio (HR) 1.17; 95% CI 1.06 to 1.29, 70 trials, N = 15,935) and some evidence that ESAs decrease overall survival (HR 1.05; 95% CI 1.00 to 1.11, 78 trials, N = 19,003). The risk ratio for thromboembolic complications was increased in patients receiving ESAs compared to controls (RR 1.52, 95% CI 1.34 to 1.74; 57 trials, N = 15,498). ESAs may also increase the risk for hypertension (fixed-effect model: RR 1.30; 95% CI 1.08 to 1.56; random-effects model: RR 1.12; 95% CI 0.94 to 1.33, 31 trials, N = 7,228) and thrombocytopenia/haemorrhage (RR 1.21; 95% CI 1.04 to 1.42; 21 trials, N = 4,507). There was insufficient evidence to support an effect of ESA on tumour response (fixed-effect RR 1.02; 95% CI 0.98 to 1.06, 15 trials, N = 5,012).
  
  
  CONCLUSIONS
  ESAs reduce the need for red blood cell transfusions but increase the risk for thromboembolic events and deaths. There is suggestive evidence that ESAs may improve QoL. Whether and how ESAs affects tumour control remains uncertain. The increased risk of death and thromboembolic events should be balanced against the potential benefits of ESA treatment taking into account each patient's clinical circumstances and preferences. More data are needed for the effect of these drugs on quality of life and tumour progression. Further research is needed to clarify cellular and molecular mechanisms and pathways of the effects of ESAs on thrombogenesis and their potential effects on tumour growth.
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Thomy
authors.initials: T
authors.lastname: Tonia
authors.forename: Annette
authors.initials: A
authors.lastname: Mettler
authors.forename: Nadège
authors.initials: N
authors.lastname: Robert
authors.forename: Guido
authors.initials: G
authors.lastname: Schwarzer
authors.forename: Jerome
authors.initials: J
authors.lastname: Seidenfeld
authors.forename: Olaf
authors.initials: O
authors.lastname: Weingart
authors.forename: Chris
authors.initials: C
authors.lastname: Hyde
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
authors.forename: Julia
authors.initials: J
authors.lastname: Bohlius
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D002423:Cause of Death; D000068256:Darbepoetin alfa; D017707:Erythrocyte Transfusion / Q000706:statistics & numerical data; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D009369:Neoplasms / Q000097:blood / Q000150:complications*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013923:Thromboembolism / Q000139:chemically induced
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa