Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anaemia is common in patients receiving chemotherapy, causing symptoms that have a major impact on quality of life (QoL). Epoetin beta rapidly increases haemoglobin (Hb) levels and improves QoL in anaemic patients with a variety of tumours. This was a randomized, double-blind, parallel-group, dose-finding study assessing the efficacy and safety of once-weekly epoetin beta in patients with solid tumours receiving chemotherapy. Adult patients with anaemia (Hb < 11 g/dL) were randomized to receive epoetin beta 30,000 IU or 20,000 IU once weekly for 12 weeks. All patients received oral iron supplementation. Haemoglobin levels, transfusion need and QoL [Functional Assessment of Cancer Therapy-fatigue (FACT-F) subscale score] were assessed at regular intervals. Fifty patients were randomized; 30 patients received epoetin beta 30,000 IU once weekly and 20 received 20,000 IU once weekly. Mean (+/- SD) increase in Hb from baseline to week 12 was 1.75 +/- 2.15 g/dL in the 30,000 IU group (P = 0.008 vs. baseline) and 1.04 +/- 1.75 g/dL in the 20,000 IU group (non-significant). Haemoglobin response (increase in Hb >or=2 g/dL from baseline) was observed in 78.3% of patients receiving epoetin beta 30,000 IU and 66.7% receiving epoetin beta 20,000 IU. Improvements in FACT-F subscale score were significantly (P < 0.001) correlated with increases in Hb level. Transfusion use was low during the study in both groups. Both epoetin beta regiments were well tolerated and there were no dose-dependent adverse events. Epoetin beta 30,000 IU once weekly is an effective and well-tolerated treatment of anaemia in patients with solid tumours.
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PMID:Once-weekly epoetin beta therapy in patients with solid tumours and chemotherapy-induced anaemia: a randomized, double-blind, dose-finding study. 1870 19

The primary aim of this study was to assess whether epoetin alpha (Ea) would improve cognitive performance in a group of anaemic cancer patients receiving chemotherapy. The secondary aim was to confirm the positive impact of Ea on haematological parameters, and quality of life (QOL). Fifty patients with solid tumours and haemoglobin (Hb) <11.0 g/dL received Ea 40,000 units once weekly for 12 weeks and were administered the Mini-Mental State Examination and the European Organization for Research and Treatment of Cancer (QLQ-C30) questionnaire prior to Ea therapy and at study completion. No clinically significant alterations were observed on cognitive function during Ea treatment. Changes in cognitive function were unrelated to Hb change and there were no significant differences in cognitive performance between Ea responders and non-responders. The analyses revealed clinically significant improvements in Hb levels, physical and role function, and clinically meaningful reductions in fatigue. Hb changes were significantly associated with the magnitude of improvement in QOL parameters. The lack of a clinical benefit in cognition observed in this study during Ea treatment may redirect the focus of research from enhancing to maintaining cognitive function, since stability in cognitive performance through time may be as well clinically important.
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PMID:Effect of epoetin alpha therapy on cognitive function in anaemic patients with solid tumours undergoing chemotherapy. 1870 21

Erythropoietin (Epo)-induced polycythemia is the main factor of adaptation to hypoxia. In this study, we analysed the effects of Epo deficiency on intrinsic functional properties of slow and fast twitch muscles in a model of erythropoietin deficient mice (Epo-TAg(h)) exposed to hypoxia. We hypothesised that Epo deficiency would be deleterious for skeletal muscle structure and phenotype, which could change its functional properties and alters the adaptive response to ambient hypoxia. Wild-type (WT) and Epo-TAg(h) mice were left in hypobaric chamber at 420 mm Hg pressure for 14 days. Soleus (SOL) and extensor digitorum longus (EDL) were analysed in vitro by mechanical measurements, immunohistological and biochemical analyses. The results were compared to those obtained in corresponding muscles of age-matched normoxic groups. Our data did not show any difference between the groups whatever the Epo deficiency and/or hypoxic conditions for twitch force, tetanic force, fatigue, typology and myosin heavy chain composition. Normoxic Epo-TAg(h) mice exhibit improved capillary-to-fibre ratio compared to WT mice in both SOL and EDL whereas no angiogenic effects of hypoxia or combined Epo-deficiency/hypoxia were observed. These results suggest that skeletal muscles possess a great capacity of adaptation to Epo deficiency. Then Epo deficiency is not a sufficient factor to modify intrinsic functional properties of skeletal muscles.
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PMID:Skeletal muscle intrinsic functional properties are preserved in a model of erythropoietin deficient mice exposed to hypoxia. 2011 84

The health-related quality of life (HRQOL) claims in the current Epoetin alfa label are based on the reanalyses of the exercise and physical function data from the Canadian Erythropoietin Study Group trial. The reanalysis was done to comply with the Food and Drug Administration's requirement of using statistical methods that are currently standard in evaluating clinical trial data. Presented here are HRQOL results associated with anemia. The Canadian Erythropoietin Study Group trial was a multicenter, double blind, randomized, placebo-controlled trial evaluating the effects of Epoetin alfa on HRQOL in anemic hemodialysis patients. A total of 118 patients who were 18-75 years old, on hemodialysis for >3 months, who had a hemoglobin <9.0 g/dL, and did not have coronary artery disease or diabetes mellitus, were randomized to either receive placebo (n=40), or receive intravenous Epoetin alfa to achieve a target hemoglobin of 9.5-11.0 g/dL (n=40) or a target of 11.5-13.0 g/dL (n=38). Patients were followed for 6 months. The two Epoetin alfa-treatment groups were combined for all analyses performed. This post hoc analysis was conducted using an intent-to-treat repeated measures mixed model analysis of variance using Bonferroni's multiplicity correction. The Epoetin alfa-treated group showed a statistically significant improvement in the Kidney Disease Questionnaire symptom of fatigue in comparison with placebo. Additionally, the change in hemoglobin at 2 months was correlated with change in fatigue, energy, shortness of breath, and weakness, but had minimal effect on depression. These analyses confirm previously reported results, which indicate that treating hemodialysis patients with an erythropoiesis-stimulating agent improves HRQOL.
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PMID:Dialysis patients treated with Epoetin alfa show improved anemia symptoms: A new analysis of the Canadian Erythropoietin Study Group trial. 2034 90

The recombinant human erythropoietins and allied proteins (epoetin alfa, attempted copies and biosimilar variants of epoetin alfa, epoetin beta, epoetin delta, epoetin zeta, epoetin theta, epoetin omega, darbepoetin alfa, and methoxy-polyethylene glycol-epoetin beta) are among the most successful and earliest examples of biotechnologically manufactured products to be used in clinical medicine. This article charts a brief history of their use in clinical medicine, mainly dealing with chronic kidney disease, paying special attention to how these agents were introduced into clinical medicine and what has happened subsequently; in 2009, there were several developments that could be regarded as a "perfect storm" in terms of the long-term use of these compounds in chronic kidney disease and oncology and, likely, elsewhere. We are now very much at a "crossroads," where mature reflection is required, because with the latest trials and meta-analyses, these therapies seem not only expensive but also very much a clinical tradeoff (increased risk of adverse effects versus a small gain in fatigue scores). How we arrived at this crossroads is a useful illustration of how easy it is, without properly designed randomized, controlled trials, to assume that clinical benefit must follow therapeutic interventions.
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PMID:2009: a requiem for rHuEPOs--but should we nail down the coffin in 2010? 2041 41

Historically, humans have long sought to enhance their "athletic" performance to increase body weight, aggressiveness, mental concentration and physical strength, contextually reducing fatigue, pain, and improving recovery. Although regular training is the mainstay for achieving these targets, the ancillary use of ergogenic aids has become commonplace in all sports. The demarcation between ergogenic aids and doping substances or practices is continuously challenging and mostly based on perceptions regarding the corruption of the fairness of competition and the potential side effects or adverse events arising from the use of otherwise unnecessary ergogenic substances. A kaleidoscope of side effects has been associated with the use of doping agents, including behavioral, skeletal, endocrinologic, metabolic, hemodynamic, and cardiovascular imbalances. Among the various doping substances, the most striking association with thrombotic complications has been reported for androgenic anabolic steroids (i.e., cardiomyopathy, fatal and nonfatal arrhythmias, myocardial infarction [MI], intracardiac thrombosis, stroke, venous thromboembolism [VTE], limb arterial thrombosis, branch retinal vein occlusion, cerebral venous sinus thrombosis) and blood boosting (i.e., VTE and MI, especially for epoetin and analogs). The potential thrombotic complication arising from misuse of other doping agents such as the administration of cortisol, growth hormone, prolactin, cocaine, and platelet-derived preparations is instead speculative or anecdotal at best. The present article provides an overview on the epidemiological association as well as the underlying biochemical and biological mechanisms linking the practice of doping in sports with the development of thrombosis.
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PMID:Doping and thrombosis in sports. 2219 57

Tumor anemia is very common in patients with cancer. The causes are very diverse and the parameter value depends on several factors. If this however develops to be symptomatic it may adversely impact health related quality of life. Erythropoietin or blood transfusion provides options for treatment. However, these are not always uneventful. There could also be a lack of response to Erythropoietin. This case report describes the complexity of tumor anemia. It also includes a more detailed discussion on the Fatigue Syndrome, which is one of the most common symptoms of patients with cancer. In the context of palliative care there is often the question of alternatives for improving the quality of patients life. Some kinds of treatment may also cause the opposite effect. A multidimensional assessment should help to approach this difficult issue and to find ways for a meaningful treatment of the symptoms of anemia.
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PMID:[Anemia caused by cancer in the context of palliative care]. 2232 49

L-Carnitine (LC) administration has been recommended for specific indications in dialysis patients, including epoetin-resistant anemia, intradialytic hypotension, cardiomyopathy, fatigue, muscle weakness, and exercise performance; it may ameliorate insulin resistance, inflammation, and protein wasting. Use of LC for anemia and intradialytic hypotension has been approved for reimbursement by the Centers for Medicare and Medicaid Services. Yet, the data to support these recommendations are inadequate and have not been bolstered over several decades. LC administration continues to appeal to nephrologists because its use in dialysis patients has an attractive rationale, it addresses problems that persist despite dialysis, it is safe, and the existing literature does not refute its use. Nevertheless, definitive trials to justify LC administration have not been conducted and are increasingly unlikely to be funded. In an era of shrinking resources and bundling of dialysis services, the use of LC in dialysis patients will, appropriately, diminish.
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PMID:L-carnitine supplementation in dialysis: treatment in quest of disease. 2317 99

Erythropoietin (Epo) is used in clinical settings to enhance hematopoietic function and to improve the quality of life for patients undergoing chemotherapy by reducing fatigue and the need for transfusions. However, several meta-analyses have revealed that Epo treatments are associated with an increased risk of mortality in cancer patients. In this study, we examined the role of Epo in prostate cancer (PCa) progression, using in vitro cell culture systems and in vivo bone metastatic assays. We found that Epo did not stimulate the proliferation of PCa cell lines, but did protect PCa cells from apoptosis. In animal models of PCa metastasis, no evidence was found to support the hypothesis that Epo enhances metastasis. Together, these findings suggest that Epo may be useful for treating severe anemia in PCa patients without increasing metastatic risk.
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PMID:Erythropoietin supports the survival of prostate cancer, but not growth and bone metastasis. 2369 92

Erythropoietin-stimulating agents (ESAs) are used in breast cancer patients with chemotherapy-induced anemia to alleviate anemia and in turn, reduce fatigue. These drugs may also decrease overall survival and increase the incidence of serious adverse effects such as thrombovascular events (TVEs). This review evaluates the evidence to date on administering ESAs to breast cancer patients with chemotherapy-induced anemia. Our findings suggest a clear need for well-designed clinical trials that follow current Food and Drug Administration (FDA) ESA label changes to guide clinical practice in an effort to reduce harm to these patients.
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PMID:Erythropoietin-stimulating agents and clinical outcomes in metastatic breast cancer patients with chemotherapy-induced anemia: a closed debate? 2455 13


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