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Anemia is a common complication in patients with hematologic malignancies, with incidence rates ranging up to 63%. In myelodysplastic syndromes, anemia is an essential feature of the disease. The decrease in hemoglobin may lead to several symptoms such as fatigue, exhaustion, and impaired quality of life, and it may worsen prognosis. Before the introduction of recombinant human erythropoietin (rHuEPO, epoetin alfa), red blood cell transfusions were the traditional treatment for improvement of Hb levels. Transfusions, however, are associated with several adverse events and risks, have only transient effects, and have a limited capacity to ameliorate the symptoms of anemia. Epoetin alfa represents a physiologic treatment option, especially in the long-term treatment of cancer- and cancer treatment-associated anemia, and is well tolerated, with response rates as high as 80%. Epoetin alfa is less effective in the treatment of the anemia of myelodysplastic syndrome, but appears to be synergistic with granulocyte-colony stimulating factor. However, not every patient responds to epoetin alfa; to avoid unnecessary interventions and costs, predictors of response have been proposed. This article outlines the advantages and disadvantages of the two major treatment forms of anemia: transfusions and epoetin alfa. Representative studies on the efficacy of epoetin alfa in anemic patients with hematologic malignancies as well as models to predict response to epoetin alfa treatment are summarized.
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PMID:Anemia of hematologic malignancies: what are the treatment options? 1208 54

Many conditions that would not be considered normal in a younger population are routinely accepted in older people as a part of so-called "normal" aging. Among these conditions are many chronic and debilitating conditions such as chronic pain, insomnia, weakness, fatigue, and anemia. This article reviews current evidence regarding the relationships among age, fatigue, weakness, anemia, and erythropoiesis. Anemia in the elderly is important because it can lead to weakness, fatigue, limitations in activity, and may increase cardiovascular risk. Recent studies of the effect of erythropoietin in an aging population support the hypothesis that anemia is associated with pathologic factors and not with normal aging. While older individuals admitted to hospitals are more likely to be anemic, these same individuals have a bone marrow mass and numbers of cultured progenitor cells that are similar to that of the younger population; therefore, the predicted response to erythropoietin, and thus the function of the bone marrow and cellular progenitors, is maintained. Thus, we can conclude that anemia is a correctable pathologic finding in elderly people. A number of studies have shown a strong relationship between fatigue and anemia, but few studies investigate to what degree age is a factor in weakness and fatigue. In a study of 375 anemic cancer patients with a median age of 61 years, age as a covariate in multiple linear regression analysis failed to reach significance for most measures of function and quality of life (QOL), including measures of energy, activities, mental health, general cancer-related QOL, and overall QOL. Additional analysis suggests that other factors, including cancer progression, hemoglobin change, and baseline hemoglobin levels, are much more important in determining change in functional and quality-of-life scores. In another set of 2,000 cancer patients and 1,000 controls, cancer patients experienced significantly more fatigue compared with controls. There was no correlation between cancer patient age and fatigue, while in controls the cohort aged 65 or more reported more fatigue than did younger subjects. Finally, measurement of QOL in the general population demonstrated, for both the Short-Form 36 and Functional Assessment of Cancer Therapy - Anemia questionnaires, that age alone is not significantly correlated with QOL. We suggest that chronic conditions such as fatigue and anemia are no more "normal" in an aging population than in a general population, and that all patients with chronic conditions be adequately treated and counseled for their condition.
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PMID:Age, anemia, and fatigue. 1208 55

Anaemia is common in patients with haematological malignancy, occurring in the majority of patients with malignant disease who are treated with chemotherapy. Most patients will have their anaemia attributed to the cytokine-mediated anaemia of chronic disease. Many of these patients with anaemia will be symptomatic with fatigue, which is the single most important symptom reported. Data from many studies indicate that treatment of patients with anaemia with recombinant human erythropoietin (rHuEpo) will increase their haemoglobin level, decrease transfusion need and also improve their quality of life. Recent clinical and experimental work suggest that improving the haemoglobin level may improve the patients' prognosis but this finding needs to be confirmed. Treatment of anaemia with rHuEpo in patients with cancer may produce many benefits. Unfortunately, rHuEpo is effective in only around 60% of patients, is slow acting and is expensive. These drawbacks have restricted its use in many healthcare systems. However, a failure to treat anaemia may have important adverse effects for the patient both in terms of their quality of life and, just possibly, in terms of their life expectancy.
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PMID:Management options for cancer therapy-related anaemia. 1209 10

Cancer-associated anemia is common and has many causes, including the effects of the underlying disease and cancer treatment. The effect of anemia on patients with cancer was not appreciated fully until relatively recently. Several well-designed studies have demonstrated the relationship between anemia and fatigue, and the effect of fatigue on quality of life. These data have resulted in a greater awareness of anemia in cancer and have increased the use of recombinant human erythropoietin (r-HuEPO, epoetin alfa) therapy for the treatment of anemia. Recombinant HuEPO produces a hemoglobin response in 50-60% of patients with cancer; however, to obtain this response rate, frequent dosing is required. Darbepoetin alfa, a recently developed erythropoietic protein, has a longer half-life than that of r-HuEPO, enabling less frequent dosing, and has a greater in vivo activity. In studies of patients with cancer who develop anemia, darbepoetin alfa has proved to be well tolerated and effective, and its advantages make it a potential improved treatment option for anemia in these patients.
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PMID:Overview of cancer-related anemia: focus on the potential role of darbepoetin alfa. 1222 85

Fatigue is one of the most common complaints of people with cancer. It affects the majority of patients actively undergoing cancer related therapies, but also a meaningful number of those who successfully completed therapy and are disease-free and potentially cured at the end of the treatments. In cancer setting, fatigue is to be defined as a chronic form of tiredness, which is perceived by the patient as being unusual or abnormal, and absolutely disproportionate with respect to the amount of exercise or activity he/she has carried out and which is not removed by resting or sleeping. The exact cause of fatigue is not known. In cancer setting there are many contributing or associated factors, such as cancer itself, cancer treatment (chemotherapy, radiation therapy, immunotherapy and surgery), depression or anxiety, some medications, pain, nausea, vomiting or diarrhea, poor nutrition, anemia, infections, insomnia. There is no standard of care for the assessment or treatment of fatigue in patients with cancer. The evaluation of fatigue is intrinsically multidimensional, even though the lack of objective measurement methods makes it difficult to draw up worldwide-accepted guidelines; nonetheless, a number of methods have been developed to assess it. Treatment of fatigue should depend on its cause, but presently it is still addressed against the associated symptoms rather than fatigue itself. Useful approaches includes erythropoietin alpha, psychostimulants, medications to treat pain, depression, nausea and difficult sleeping, physical therapy for reconditioning exercises or energy saving techniques, health education. In this report some of the crucial issues related to fatigue in people with cancer are reviewed.
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PMID:Cancer-related fatigue (review). 1237 Jul 60

The clinical development of recombinant human erythropoietin (rHuEPO) has had a remarkable impact on the clinical practice of oncology. A decade ago, randomized, placebo-controlled trials in anemic cancer patients demonstrated that rHuEPO resulted in an improvement in hemoglobin and hematocrit, a reduction in transfusion requirements, and improvement in quality-of-life (QOL) end points. Based on these trials, recombinant erythropoietin was approved for the treatment of anemia in patients with nonmyeloid malignancies in whom the anemia was caused by the effect of chemotherapy. The clinical indication was to decrease the needfor transfusion in patients for whom anemia was not due to other reversible causes. Despite this broad indication, the incorporation of rHuEPO in clinical practice was limited because of a variety of factors, including physician perception that mild-to-moderate anemia in the cancer patient was generally asymptomatic and did not warrant intervention. Subsequently, three large open-label, prospective trials of recombinant erythropoietin were performed in the community setting in anemic cancer chemotherapy patients. All three trials replicated the results of the original randomized study, but with a much larger database of more than 7,000 patients. Importantly, these trials were able to define the major impact of hemoglobin level on quality of life. Patients on these trials who improved their hemoglobin > 2 g/dL or achieved a hemoglobin > or = 12 g/ dL had the greatest improvement in symptoms of energy, activities of daily living, and overall quality of life. Furthermore, a once-per-week dosing schedule was found to be comparable to three-times-weekly administration of rHuEPO. A European randomized, placebo-controlled trial confirmed these QOL results, and a meta-analysis of other randomized clinical trials firmly supports the role of erythropoietin therapy in improving hemoglobin levels and reducing transfusion requirements. Based on this aggregate of data, the use of erythropoietin in the treatment of mild-to-moderate anemia has become a standard of care. These studies have also expanded our understanding of the problem of fatigue and the study of interventions that can improve quality of life for cancer patients.
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PMID:Recombinant human erythropoietin in cancer-related anemia. Review of clinical evidence. 1238 Sep 54

Fatigue is an extraordinarily common consequence of cancer and its treatment. Fatigue can result in diminished cognitive and physical functional capacity and may be the result of multiple causes. However, aside from psychological factors, the main physiological factors leading to fatigue in cancer patients are anemia, severe deconditioning, and muscle wasting that is secondary to cachexia. One of the most common measures of functional capacity is maximal aerobic capacity, also called VO2max. VO2max is a measurement of the maximal capacity of the entire cardiorespiratory system and muscles to consume oxygen. It is strongly predictive of functional status, and it is strongly related to circulating hemoglobin. Research has indicated that the use of recombinant human erythropoietin to treat anemia can preserve or increase VO2max. In addition, aerobic exercise training has been demonstrated to greatly relieve symptoms of fatigue in patients with cancer. It is both safe and effective in this patient population. Muscle wasting results in diminished protein reserve and extreme muscle weakness. Progressive resistance exercise training has been demonstrated to greatly increase strength, improve protein balance, and increase muscle mass even in very frail and old men and women. It should be strongly encouraged in patients experiencing muscle wasting and weakness. A comprehensive "cancer rehabilitation"program is described, which is made up of (1) correcting anemia related to cancer or its treatment; (2) aerobic conditioning to improve VO2max; and (3) progressive resistance exercise in patients experiencing muscle weakness or wasting. In this way, the physiological causes of fatigue may be addressed and quality of life improved.
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PMID:Physical function in men and women with cancer. Effects of anemia and conditioning. 1238 Sep 60

Anemia, common in people with cancer, can be due to the disease itself or to the associated therapy. Fatigue, the most prevalent of all symptoms experienced by cancer patients, is the primary symptom of anemia. Caused by many factors,fatigue, regardless of etiology, has an adverse impact on health-related quality of life. Anemia is among the more treatable of those causes. Prior to the development of recombinant human erythropoietin, red blood cell transfusion was the standard treatment for cancer-related anemia. Erythropoietic agents are an effective alternative to blood transfusion: they improve hematocrit, reduce transfusion dependency, and eliminate transfusion-related risks. Although studies are mixed, most clinical trials have also suggested that erythropoietic agents have a positive impact upon cancer patients' quality of life. However, the cost of drug supply is quite high in the oncology setting, where much higher doses are required relative to the nephrology setting. Thus, although few challenge the treatment's effectiveness, cost-effectiveness remains an open question. The data collected over the years to address these questions have helped define and clarify the relationship between anemia and health-related quality of life in people with cancer. That relationship is summarized in this article.
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PMID:The effects of anemia and anemia treatment on the quality of life of people with cancer. 1238 Sep 62

Anemia is prevalent among cancer patients with hematologic malignancies, with fatigue and weakness, major symptoms of anemia, contributing to diminished quality of life (QOL). Data from several randomized, placebo-controlled clinical trials and three large community-based studies in patients with hematologic malignancies indicate that recombinant human erythropoietin (r-HuEPO, epoetin alfa) can correct anemia, reduce transfusion requirements, and improve QOL. Moreover, a positive relationship has been found between increased hemoglobin (Hb) levels and improvements in QOL assessments, regardless of disease state, with the greatest incremental improvement occurring when Hb increases from 11 g/dL to 12 g/dL (range, 11 to 13 g/dL). This suggests that patients with mild-to-moderate anemia may achieve the greatest QOL benefit from epoetin alfa therapy. Evidence from community-based studies suggests that epoetin alfa administered once weekly has a similar safety and efficacy profile as three-times-weekly administration. Further research is ongoing with less frequent dosing regimens. The beneficial effects of epoetin alfa therapy have been reported in studies involving patients with chronic lymphocytic leukemia (CLL), multiple myeloma, and lymphomas. Evidence also exists that epoetin alfa can benefit patients with myelodysplastic syndromes (MDS), although these results have not been as impressive. Combining epoetin alfa with other cytokine growth factors may confer some additional benefit in these patients, but more rigorous investigation is required.
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PMID:Epoetin alfa as a supportive measure in hematologic malignancies. 1244 49

Many cancer patients suffer from anemia, which has a major detrimental effect on their quality of life. Recombinant human erythropoietin (rHuEPO) is now widely used in cancer patients, as it improves hematocrit, lowers blood transfusion requirements, and improves quality of life. Recent research indicates that EPO has pleiotropic effects on the body well beyond the maintenance of red cell mass, but the mechanisms involved in relieving fatigue and improving quality of life in cancer patients are poorly understood. EPO receptors (EPO-Rs) have been detected in many different cells and tissues, providing evidence for autocrine, paracrine, and endocrine functions of EPO. Apart from its endocrine function, EPO may have a generalized role as an antiapoptotic agent that is associated with enhancement of muscle tone, mucosal status, and gonadal and cognitive function. The recent discovery of EPO-Rs in breast tumor vasculature, while raising important questions about the possible effects of pharmacological doses of rHuEPO on tumor cells, also suggests that the receptors could provide a useful target for drugs attached to EPO.
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PMID:EPO's alter ego: erythropoietin has multiple actions. 1245 56


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