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 · 2.45 Impact Factor
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- "Adverse events associated with ESAs are multifactorial in origin. Anaemic patients with cancer who are treated with ESAs show evidence of increased frequency of thrombotic events (Bohlius et al., 2006). Severe elevation in haematocrit (HbDhaematocrit divided by 3) in haemodialysis patients treated with ESAs is associated with hypertension, thromboembolism and decreased survival (Regidor et al., 2006). "
ABSTRACT: Oxygen is essential for life, and the body has developed an exquisite method to collect oxygen in the lungs and transport it to the tissues. Hb contained within red blood cells (RBCs), is the key oxygen-carrying component in blood, and levels of RBCs are tightly controlled according to demand for oxygen. The availability of oxygen plays a critical role in athletic performance, and agents that enhance oxygen delivery to tissues increase aerobic power. Early methods to increase oxygen delivery included training at altitude, and later, transfusion of packed RBCs. A breakthrough in understanding how RBC formation is controlled included the discovery of erythropoietin (Epo) and cloning of the EPO gene. Cloning of the EPO gene was followed by commercial development of recombinant human Epo (rHuEpo). Legitimate use of this and other agents that affect oxygen delivery is important in the treatment of anaemia (low Hb levels) in patients with chronic kidney disease or in cancer patients with chemotherapy-induced anaemia. However, competitive sports was affected by illicit use of rHuEpo to enhance performance. Testing methods for these agents resulted in a cat-and-mouse game, with testing labs attempting to detect the use of a drug or blood product to improve athletic performance (doping) and certain athletes developing methods to use the agents without being detected. This article examines the current methods to enhance aerobic performance and the methods to detect illicit use.British Journal of Pharmacology 07/2008; 154(3):529-41. DOI:10.1038/bjp.2008.89 · 4.99 Impact Factor
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- "Cancer-related and chemotherapy-induced anemia negatively impacts the quality of life of many cancer patients and is accompanied by a poor prognosis [1 – 5]. Therefore, anemia is frequently corrected by blood transfusions or application of erythropoiesis-stimulating agents (ESAs) . However, three randomized clinical studies reported a negative impact of ESAs on overall survival and local tumor control in breast , head and neck , and non – small cell lung cancer patients . "
ABSTRACT: Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required. Cancer recurrence is thought to rely on the proliferation of cancer initiating cells (CICs). In breast cancer, CICs can be identified by phenotypic markers and their fate is controlled by the Notch pathway. In this study, we investigated the effect of erythropoietin on CICs in breast cancer cell lines. Levels of erythropoietin receptor (EpoR), CD24, CD44, Jagged-1 expression, and activation of Notch-1 were assessed by flow cytometry. Self-renewing capacity of CICs was investigated in sphere formation assays. EpoR expression was found on the surface of CICs. Recombinant human Epo (rhEpo) increased the numbers of CICs and self-renewing capacity in a Notch-dependent fashion by induction of Jagged-1. Inhibitors of the Notch pathway and PI3-kinase blocked both effects. Erythropoietin functionally affects CICs directly. Our observation may explain the negative impact of recombinant Epo on local control and survival of cancer patients with EpoR-positive tumors.Neoplasia (New York, N.Y.) 01/2008; 9(12):1122-9. DOI:10.1593/neo.07694 · 5.40 Impact Factor