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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a clear relationship between anaemia and cardiovascular risk in chronic renal failure (CRF) patients. Left ventricular hypertrophy (LVH) is present in about three-quarters of patients starting dialysis, and is a strong predictor of mortality. Anaemia contributes to the development of LVH, mainly via increased cardiac output. In some patients, anaemia results in an increase in LV mass, while in others it also results in LV end-diastolic volume dilatation. These changes increase the risk of arrhythmias, myocardial infarction and myocardial fibrosis. The lower the haemoglobin, the more likely it is that LVH and heart failure will develop. Furthermore, a haemoglobin of < 11 g/dl is associated with increased morbidity and mortality. Partial correction of anaemia with epoetin leads to a partial, but not complete, reversal of LVH. One large prospective study (Lombardy Registry) found that epoetin treatment was accompanied by a 30% reduction in crude relative risk of mortality. A progressive reduction in the relative risk of general and cardiovascular mortality was found with increasing haematocrit, with and without adjustment for co-morbid conditions. Mean hospitalizations also decreased with increasing haematocrit. The long-term effects of normalized haematocrit/haemoglobin values in uraemic patients have not yet been evaluated exhaustively in prospective, randomized, multicentre studies. Epoetin treatment has been shown to induce lasting improvements in patients' sense of well-being, reduce fatigue, increase appetite and work capacity, and improve exercise tolerance, libido and work performance. Further studies are needed to demonstrate whether greater haemoglobin concentrations are associated with greater improvements in quality of life during epoetin treatment.
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PMID:What are the short-term and long-term consequences of anaemia in CRF patients? 1033 65

Anaemia is a common occurrence in patients with cancer and contributes to the clinical symptomatology and reduced quality of life (QOL) seen in cancer patients. Many aspects of reduced QOL, including fatigue, are known to be associated with suboptimally low levels of haemoglobin. Even mild-to-moderate anaemia adversely affects patient-reported QOL parameters. Red blood cell transfusions are associated with many real and perceived risks, inconveniences, costs, and only temporary benefits. Recombinant human erythropoietin (rHuEPO) is an effective therapy to increase haemoglobin values in over half of anaemic cancer patients receiving concurrent chemotherapy. These increased haemoglobin values are closely correlated with improvements in QOL. Despite these objectively defined benefits, less than 50% of anaemic patients undergoing cytotoxic chemotherapy receive rHuEPO, in contrast to patients with chronic renal failure on dialysis, where anaemia is universally and aggressively treated to more optimal haemoglobin values. However, there are several barriers that may limit more widespread use of rHuEPO. These include inconvenience associated with frequent dosing; failure of a large proportion (40 to 50%) of patients to respond; relatively slow time to response; absence of reliable early indicators of response; and current lack of rigorous pharmacoeconomic data demonstrating cost-effectiveness. Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP) that is biochemically distinct from rHuEPO, and which has been proven to stimulate red blood cell production. The molecule has a 3-fold longer half-life and increased biological activity that will allow less frequent dosing, facilitating improved management of the anaemia of cancer. With this new option for therapy, further avenues of investigation should lead to renewed interest in the clinical benefits of optimal haemoglobin levels for patients with cancer.
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PMID:Anaemia and its functional consequences in cancer patients: current challenges in management and prospects for improving therapy. 1130 72

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

This article examines the relationships between chemotherapy-induced anemia, fatigue, and psychological distress among anemic cancer patients with solid tumors. Patients participating in two randomized clinical trials evaluating the efficacy of darbepoetin alfa (Aranesp) completed a questionnaire at baseline, at the beginning of each chemotherapy cycle, and at the end of the 12-week treatment period. The questionnaire included four psychological distress outcomes: Brief Symptom Inventory (BSI) Depression and Anxiety, Functional Assessment of Cancer Therapy (FACT)-Emotional Well-Being, numeric rating scale of Overall Health, and the FACT-Fatigue subscale. Patients with a hemoglobin response of at least a 2 g/dL increase were more likely to experience meaningful improvements (at least 3 points) in FACT-Fatigue scores than nonresponders (55.0% vs 39.8%; P = .0004). Patients with meaningful improvements in FACT-Fatigue scores reported significantly greater improvements in each of the psychological outcomes relative to those without improved fatigue (P <.0001). For BSI Depression and Anxiety, the differences in mean change scores between patients with and without improved fatigue were 8.2 and 7.7, respectively. Improving the hemoglobin levels of patients undergoing chemotherapy and suffering from anemia-related fatigue has the potential to produce significant positive effects on patients' fatigue, depressive symptoms, anxiety, feelings of helplessness, and overall health.
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PMID:Psychological outcomes associated with anemia-related fatigue in cancer patients. 1238 Sep 61

Darbepoetin alfa, novel erythropoiesis stimulating protein closely related to human erythropoietin, has been developed for the treatment of chemotherapy-related anaemia in patients with non-myeloid malignancies. In three 12-week, phase II studies in patients with cancer and chemotherapy-related anaemia, subcutaneous darbepoetin alfa, administered in once-weekly or 2-, 3- or 4-weekly regimens, dose-dependently increased the mean haemoglobin levels. In a randomised, double-blind, phase III study in 320 patients with lung cancer and chemotherapy-related anaemia, recipients of subcutaneous darbepoetin alfa 2.25 micro g/kg once weekly, received red blood cell (RBC) transfusion approximate, equals 2-fold less frequently than placebo recipients (p < 0.001). In the same study, patients receiving darbepoetin alfa also received fewer standard units of RBC for transfusion and had greater haematopoietic response rate than placebo recipients (both p < 0.001). Subcutaneous darbepoetin alfa 2.25 micro g/kg once weekly also reduced patient-reported fatigue (assessed by a quality-of-life questionnaire) [p = 0.019 vs placebo]. black triangle Darbepoetin alfa was generally well tolerated in clinical trials. The most frequent darbepoetin alfa-related adverse events were: body oedema, arthralgia and skin rash.
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PMID:Darbepoetin alfa: in patients with chemotherapy-related anaemia. 1274 34

Neutropenia and anaemia are serious complications of myelosuppressive chemotherapy. They have a negative impact on patient quality of life and may reduce response to treatment. Febrile neutropenia, a potentially life-threatening complication of neutropenia, frequently requires hospital admission, while fatigue and weakness from anaemia reduce patient's capacity for activity. Pegfilgrastim and darbepoetin alfa, were designed to simplify and optimise treatment for patients with cancer. Once-per-cycle pegfilgrastim is as effective as daily filgrastim with respect to duration of severe neutropenia (DSN) and may have a lower incidence of febrile neutropenia than filgrastim. Darbepoetin alfa has enhanced biological activity and a serum terminal half-life three-fold longer than that of erythropoietin (EPO), which translates into rapid and sustained correction of anaemia with less frequent dosing. These novel cytokines have the potential to simplify the management of neutropenia and anaemia with fewer injections and less disruption to patients daily lives.
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PMID:Optimising management of neutropenia and anaemia in cancer chemotherapy-advances in cytokine therapy. 1456 20

The objective of this ongoing trial is to study the ability of darbepoetin alfa to reverse chemotherapy-induced anemia in cancer patients, and to relate improvement in hemoglobin with changes in fatigue and functional capacity. Eligible subjects had a nonmyeloid malignancy, were receiving multicycle chemotherapy, and were anemic, as defined by a screening hemoglobin < or = 11 g/dL. Darbepoetin alfa was administered at a starting dosage of 3 microg/kg every 2 weeks for up to eight doses (16 weeks) in an open-label, noncomparative setting. A total of 194 oncology practices contributed 1,173 subjects to this interim analysis. The mean increase in hemoglobin was 1.7 g/dL (95% CI: 1.6, 1.8) to last value on study (intent-to-treat analysis) and 2.1 g/dL (95% CI: 1.9, 2.2) for those patients receiving the full 16 weeks of therapy. The Kaplan-Meier estimate of the proportion of subjects with a hematopoietic response (increase in hemoglobin > or = 2 g/dL and/or hemoglobin value > or = 12 g/dL) was 84% (95% CI:81,86). Subjects in the lower baseline hemoglobin category (< 10 g/dL) tended to have a greater hemoglobin response during treatment. The Functional Assessment of Cancer Therapy-Fatigue (FACT-Fatigue) subscale score increased by a mean of 6.8 points (26%) during the study, and improvements in fatigue paralleled the increases observed in hemoglobin. Study treatment-related toxicity was minimal, with the most common event being injection-site pain, seen in 2% of subjects. Experience to date with an every-2-week regimen of darbepoetin alfa indicated efficacy comparable to historical experience with weekly and 3-times-weekly regimens of epoetin alfa in treating chemotherapy-induced anemia in cancer subjects.
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PMID:Assessment of hematologic effects and fatigue in cancer patients with chemotherapy-induced anemia given darbepoetin alfa every two weeks. 1535 56

Anaemia is highly prevalent in patients with cancer, and its incidence and severity depend on many factors, such as type of anti-cancer therapy. The decreased oxygen capacity of blood resulting from anaemia affects virtually every organ and tissue system in the body, manifesting in numerous signs and symptoms that include fatigue, dyspnoea, palpitations, tachycardia, asthenia, anorexia, cold hypersensitivity and general weakness. Anaemia related to cancer may also cause cognitive dysfunction, leading to decreased mental alertness, poor concentration and memory problems. There is a close association between anaemia and overall quality of life (QoL) variables, and anaemia is an adverse prognostic factor in patients with cancer. Since anaemia can seriously compromise the QoL of cancer patients and is associated with decreased overall survival time, there is a strong need for effective and well-tolerated treatment strategies. Erythropoietic agents have been proven to be safe, well-tolerated and effective in the management of anaemia in patients with cancer. Epoetin therapy reduces transfusion requirements and increases haemoglobin levels in patients with solid tumours and haematological malignancies.
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PMID:The burden of anaemia in patients with cancer. 1548 59

Anemia occurring in patients with renal failure on dialysis has been shown to both increase transfusion requirements and decrease functional status and quality of life. As a result, treatment of these patients with an erythropoietic agent such as epoetin alfa or darbepoetin alfa has become established as an essential part of optimal patient care. Anemia resulting from cancer or chemotherapy is a common problem in oncology, and has been shown similarly to increase transfusion risk and decrease patient reported outcomes. For reasons that are not clear, but may include either frequently encountered slow response or nonresponse and higher doses and hence higher costs, treatment of anemia in oncology has not become a standard treatment for all patients. Erythropoietic agents (epoetin alfa and darbepoetin alfa) have been used to improve anemia-related fatigue and quality of life in cancer patients. Epoetin is administered 1 to 3 times per week whereas darbepoetin, with up to a 3-fold greater half-life, is given once every 1 or 2 weeks. Recent data demonstrate that darbepoetin can be administered as infrequently as every 3 weeks with comparable erythropoietic efficacy. Several studies have been carried out to determine the optimum schedule of dosing to obtain maximum patient benefit. Following treatment with darbepoetin, antibodies to darbepoetin were not detected, no unusual adverse event was seen with darbepoetin, and the mean increase in hemoglobin remained unchanged when the dosing interval was increased from 1 to 2 weeks. The safety and efficacy of darbepoetin was also determined in patients with solid tumors receiving chemotherapy; the lowest clinically effective dose was determined to be 3.0 and 5.0 microg/kg every 2 weeks with a 66 and 84% response, respectively. No additional benefit was seen with higher doses. A multicenter study evaluated the safety and efficacy of darbepoetin administered either weekly, every 3 weeks, or every 4 weeks in anemic patients with cancer who were not receiving chemotherapy or radiotherapy. The results indicated that with weekly dosing, 70% of patients showed an increase in hemoglobin. The dose of 4.5 microg/kg/week resulted in 100% hematopoietic response. In a randomized, active control, pilot trial, front-loading darbepoetin followed by lower doses or less frequent doses also appears to be efficacious and may decrease the time to response. At the present time, darbepoetin improves anemia, reduces requirements for transfusion, and improves the quality of life for these patients. To compare efficacy of these erythropoietic agents it is important to analyze the data using intent to treat rather than analysis of patients who complete the study. This way a true evaluation of the change of hemoglobin can be assessed corresponding both to dose and an improvement in the QOL.
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PMID:Phase III clinical trials with darbepoetin: implications for clinicians. 1579 14

We evaluated Darbepoetin alpha (Aranesp; Amgen), a novel erythropoietic protein, in patients who developed anemia while receiving chemotherapy. Seventy-five patients (median age 62 years, range 40-81 years) undergoing different cancer chemotherapy regimens were treated with darbepoetin alpha. Therapy was started if hemoglobin (Hb) levels fell below 10 g/dl or if symptomatic anemia developed. Treatment effect was evaluated after 4 weeks, 8 weeks and at the end of therapy (up to 12 weeks). If no increase in Hb was seen after 4 weeks, the dose of darbepoetin alpha was increased to 300 microg. Patients were questioned about fatigue and any change during treatment, with evaluation according to a four-point scale, where 0 = no fatigue and 3 = severe fatigue. We observed a treatment response in 54 of 75 patients (72%). Dose escalation was necessary in 30 of 75 patients (40%) and blood transfusions were required in 13 of 75 patients (17.3%). Response was observed in 32 of 43 patients (74.4%) who had a baseline Hb < 10 g/dl and in 22 of 32 (68.8%) patients who had a baseline Hb > or =10 g/dl. At baseline, 60 of 75 patients (93.3%) reported fatigue of grade 2 or 3, but at the end of the 12-week follow-up period, only 26 of 68 patients (38.3%) reported fatigue at these levels. We conclude that darbepoetin alpha is a highly effective and well-tolerated drug in the treatment of chemotherapy-associated anemia. Patients benefited both in terms of Hb levels and control of chemotherapy-related symptoms.
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PMID:Darbepoetin alpha as treatment for anemia in patients receiving chemotherapy: a single-center experience. 1593 Aug 88


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