Erythropoietin or Darbepoetin for patients with cancer
Julia Bohlius1, JayneWilson2, Jerome Seidenfeld3, Margret Piper3, Guido
Schwarzer4, Josie Sandercock5, Sven Trelle6, OlafWeingart
1, Susan Bayliss7, Susan Brunskill8, Benjamin Djulbegovic9, Charles Bennett10,
Simon Langensiepen11 , Chris Hyde8, Andreas Engert
1Cochrane Haematological Malignancies Group, Department I of Internal
Medicine, University Hospital of Cologne, Cologne,
Germany. 2Dep. Public Health, University of Birmingham, Birmingham, UK.
3Technology Evaluation Center, Blue Cross and Blue
Shield Association, Chicago, IL, USA. 4Department ofMedical Biometry and
Statistics, German Cochrane Center, Freiburg, Germany.
5Dep Public Health, University of Birmingham, Birmingham, UK. 6Division of
Clinical Epidemiology and Biostatistics, Institute of
Social and PreventiveMedicine,University of Bern, Bern, Switzerland. 7Dep
PublicHealth and Epidemilogy,University of Birmingahm,
Birmingham, UK. 8Systematic Review Initiative, NHS Blood and Transplant,
Oxford, UK. 9Department of Oncology, H. Lee Moffit
Cancer Center and Research Institute, Tampa, Florida, USA. 10Health Services
Research and Development Program, VA Chicago
Health Care System-Lakeside Division, Chicago, Illinois, USA. 11Department of
Internal Medicine I, University of Cologne, 50924
Contact address: Julia Bohlius, CochraneHaematologicalMalignancies
Group,Department I of InternalMedicine, UniversityHospital
of Cologne, Kerpener Str. 62, Cologne, 50924, Germany. julia.bohlius@uk-
Editorial group: Cochrane Haematological Malignancies Group.
Publication status and date: Edited (no change to conclusions), published in
Issue 1, 2009.
Review content assessed as up-to-date: 23 May 2006.
Citation: Bohlius J, Wilson J, Seidenfeld J, Piper M, Schwarzer G, Sandercock
J, Trelle S, Weingart O, Bayliss S, Brunskill S,
Djulbegovic B, Bennett C, Langensiepen S, Hyde C, Engert A. Erythropoietin or
Darbepoetin for patients with cancer. Cochrane
Database of Systematic Reviews 2006, Issue 3. Art. No.: CD003407. DOI:
Copyright © 2009 The Cochrane Collaboration. Published by JohnWiley & Sons,
A B S T R A C T
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.
The aim of this systematic review was to assess the effects of Epo or Darbepo to
either prevent or treat anaemia in cancer patients.
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
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.
Data collection and analysis
Several review authors independently assessed trial quality and extracted data.
Erythropoietin or Darbepoetin for patients with cancer (Review) 1
Copyright © 2009 The Cochrane Collaboration. Published by JohnWiley &
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).
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.
P L A I N L A N G U A G E S U M M A R Y
Erythropoietin (Epo) or darbepoetin (Darbepo) reduce transfusions in anaemic
cancer patients but increase the risk for thrombotic
complications. Whether Epo/Darbepo effects survival is uncertain.
Blood transfusions are one choice of treatment for severe cancer-related
anaemia, i.e. haemoglobin level below 8 g/dl. Human erythropoietin
is a glycoprotein hormone produced in the kidney. Recombinant human
erythropoietin is used to prevent and treat anaemia in
cancer patients. This review showed consistent evidence that Epo/Darbepo
reduces the risk for blood transfusions and the number of
units transfused in anaemic cancer patients. Quality of life might be improved
following Epo/Darbepo treatment. However, the risk for
thrombotic complications is increased and it remains uncertain whether and how
Epo/Darbepo effects tumour control and survival.
In twenty-one studies, erythropoietin was given in a fixed dose
either once or three times per week. The cumulative weekly dose
ranged from 30,000 U to 70,000 IU. Several studies compared
different erythropoietin dosages, e.g. 450 versus 900 IU/kg body
weight per week (Ten Bokkel 1998, Thatcher 1999) or 300 versus
600 IU/kg body weight per week (Kunikane 2001). Overall the
cumulative dosages ranged from 300 IU/kg per week to 1,200 IU Download full-text
/kg per week. The dosages in the darbepoetin studies ranged from
1.0 μg/kg per week to 5 μg/kg per week. Schemes for administration
ranged from once per week to once every four weeks. In the
darbepoetin studies, three (Hedenus 2002; Smith 2003) or six (
Kotasek 2003) different dosage arms were compared to one control
group. A minimum dosage for darbepoetin was not required