Erythropoietin or Darbepoetin for patients with cancer
ABSTRACT 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 pharmaceutical companies.
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.
Several reviewers independently assessed trial quality and extracted data.
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.
Full-textDOI: · Available from: Benjamin Djulbegovic, Dec 19, 2013
- SourceAvailable from: Jan Hendrik Duedal Rölfing
- "The authors concluded that insufficient data exist to support an effect of ESAs on tumor progression (RR 1.02, 95% CI 0.98–1.06) and warrant further research into cellular mechanisms and pathways (Tonia et al. 2012). Hence, the matter of debate whether EPO can promote tumor growth and induces cancer-therapy resistance continues (Jelkmann 2007). "
Article: The effect of erythropoietin on boneActa Orthopaedica 02/2014; 85(S353):1-29. DOI:10.3109/17453674.2013.869716 · 2.77 Impact Factor
- "Clinical trials with ESAs have reported an improved QoL and decreased treatment-related anemia (including numbers of blood transfusions) . Other studies suggested an improvement in survival outcome of cancer patients that received rHuEPO for anemia . "
Article: Erythropoietin update 2011[Show abstract] [Hide abstract]
ABSTRACT: Traditionally, erythropoietin (EPO) is described as a hematopoietic cytokine, regulating proliferation and differentiation and survival of the erythroid progenitors. The recent finding of new sites of EPO production and the wide spread distribution of EPO receptors (EPO-R) on endothelial cells, cardiomyocytes, renal cells as well as the central and peripheral nervous system raised the possibility that EPO may exert pleiotropic actions on several targets. Indeed studies (mainly preclinical) have documented protective, non-hematopoietic, abilities of EPO in a variety of tissue. However, the data obtained from clinical studies are more skeptical about these properties. This article provides a comprehensive overview of EPO and its derivatives.Medical science monitor: international medical journal of experimental and clinical research 11/2011; 17(11):RA240-247. DOI:10.12659/MSM.882037 · 1.43 Impact Factor
[Show abstract] [Hide abstract]
- "The use of EPO has been shown to worsen outcome in certain cancers due to increased thromboembolic risk and possibly EPO-induced tumour progression . This observation raises concerns over EPO use in patients with malignancies who develop sepsis. "
ABSTRACT: Sepsis is the systemic inflammatory response to infection and can result in multiple organ dysfunction syndrome with associated high mortality, morbidity and health costs. Erythropoietin is a well-established treatment for the anaemia of renal failure due to its anti-apoptotic effects on red blood cells and their precursors. The extra-haemopoietic actions of erythropoietin include vasopressor, anti-apoptotic, cytoprotective and immunomodulating actions, all of which could prove beneficial in sepsis. Attenuation of organ dysfunction has been shown in several animal models and its vasopressor effects have been well characterised in laboratory and clinical settings. Clinical trials of erythropoietin in single organ disorders have suggested promising cytoprotective effects, and while no randomised trials have been performed in patients with sepsis, good quality data exist from studies on anaemia in critically ill patients, giving useful information of its pharmacokinetics and potential for harm. An observational cohort study examining the microvascular effects of erythropoietin is underway and the evidence would support further phase II and III clinical trials examining this molecule as an adjunctive treatment in sepsis.Critical care (London, England) 08/2010; 14(4):227. DOI:10.1186/cc9049 · 4.48 Impact Factor