Erythropoietin or darbepoetin for patients with cancer.
BACKGROUND
Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoietin (Epo), darbepoetin (Darbepo) and red blood cell transfusions.


OBJECTIVE
The aim of this systematic review was to assess the effects of Epo or Darbepo to either prevent or treat anaemia in cancer patients.


METHODS
We searched the Central Register of Controlled Trials, MEDLINE and EMBASE and other data bases. Searches were done for the periods 01/1985 to 12/2001 for the first review and 1/2002 to 04/2005 for the update. We also contacted experts in the field and pharmaceutical companies.


METHODS
Randomised controlled trials on managing anaemia in cancer patients that compared the use of Epo/Darbepo (plus transfusion if needed) with observation until red blood cell transfusion was required.


METHODS
Several reviewers independently assessed trial quality and extracted data.


RESULTS
This update of the systematic review included a total of 57 trials with 9,353 patients. Of these, 27 trials with 3,287 adults were also included in the first Cochrane Review. Thirty trials with 6,066 patients were added during the update process. Use of Epo/Darbepo significantly reduced the relative risk of red blood cell transfusions (RR 0.64; 95% CI 0.60 to 0.68, 42 trials, n = 6,510). On average participants in the Epo/Darbepo group received one unit of blood less than the control group (WMD -1.05; 95% CI -1.32 to -0.78, 14 trials, n = 2,353). For participants with baseline haemoglobin below 12 g/dL haematological response was observed more often in participants receiving Epo/Darbepo (RR 3.43; 95% CI 3.07 to 3.84, 22 trials, n = 4,307). There was suggestive evidence that Epo/Darbepo may improve Quality of Life (QoL). The relative risk for thrombo embolic complications was increased in patients receiving Epo/Darbepo compared to controls (RR 1.67, 95% CI 1.35 to 2.06; 35 trials, n = 6,769). Uncertainties remain whether and how Epo/Darbepo effects tumour response (fixed effect RR 1.12; 95% CI 1.01 to 1.23, 13 trials, n = 2,833; random effects: RR 1.09; 95% CI 0.94 to 1.26) or overall survival (unadjusted and adjusted data: HR 1.08; 95% CI 0.99 to 1.18; 42 trials, n = 8,167).


CONCLUSIONS
There is consistent evidence that administration of Epo/Darbepo reduces the relative risk for blood transfusions and the number of units transfused in cancer patients. For patients with baseline haemoglobin below 12 g/dL (mild anaemia) there is strong evidence that Epo/Darbepo improves haematological response. There is suggestive evidence that Epo/Darbepo may improve QoL. However, there is strong evidence that Epo/Darbepo increases the relative risk for thrombo embolic complications. Whether and how Epo/Darbepo effects tumour response and overall survival remains uncertain.
Bohlius
J
J
University Hopsital, Cologne University, Department I for Internal Medicine, Cologne, Germany, D 50924. julia.bohlius@uk-koeln.de
Wilson
J
J
Seidenfeld
J
J
Piper
M
M
Schwarzer
G
G
Sandercock
J
J
Trelle
S
S
Weingart
O
O
Bayliss
S
S
Brunskill
S
S
Djulbegovic
B
B
Benett
C L
CL
Langensiepen
S
S
Hyde
C
C
Engert
E
E
D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D000068256:Darbepoetin alfa; D017707:Erythrocyte Transfusion / Q000706:statistics & numerical data; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000150:complications*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa