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 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

We report a 3-year case history that describes a 78-year-old woman with recurrent transfusion-dependent pure red cell aplasia (PRCA) secondary to recombinant epoetin use that was responsive to immunosuppressant therapy. The patient had kidney disease of unknown aetiology (estimated glomerular filtration rate of 13 ml/min/1.73 m2) and was not on dialysis. After 16 months of therapy with subcutaneous Eprex, she developed anti-erythropoietin antibody-confirmed PRCA and was started on high dose prednisone (50 mg per day). Within 5 months, the patient's serum was clear of antibodies and, under the cover of low dose prednisone (5-7.5 mg per day), therapy with a different erythropoiesis-stimulating compound (Aranesp) was initiated due to persistent fatigue and anaemia. At 3 months of therapy, the serum anti-erythropoietin antibodies remained negative and, due to the patient's requests, and after discussion, prednisone therapy was discontinued. Unfortunately, 3 months after cessation of prednisone, a recurrence of PRCA was confirmed by the development of profound anaemia and reappearance of anti-erythropoietin antibodies in the patient's serum. High dose prednisone (50 mg per day) was reinstituted, whereupon, 2 months later, antibodies were again confirmed to be negative. This case report demonstrates the responsiveness of PRCA to simple immunosuppressive therapy, and the ability to introduce different erythropoiesis-stimulating agents in the presence of such therapy. It appears that there may be problems associated with discontinuation of immunosuppressive therapy in the presence of sustained erythropoiesis-stimulating agent therapy in those in whom the condition has occurred previously.
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PMID:Successful reintroduction of a different erythropoiesis-stimulating agent after pure red cell aplasia: relapse after successful therapy with prednisone. 1604 10

(1) Current treatments for anaemia in patients receiving cancer chemotherapy include blood transfusion and epoetin alfa and beta. These epoetins correct anaemia in 40% to 65% of patients and reduce the number of patients who require transfusions during the second and third months of treatment by 12-35% in absolute terms. (2) Darbepoetin alfa is slightly more glycosylated than epoetin alfa and beta. It is no more effective than these two drugs in chronic renal failure. Darbepoetin alfa is now approved for the treatment of anaemia in patients who are receiving chemotherapy for non myeloid malignancies. (3) Two placebo-controlled dose-finding studies and two placebo-controlled trials involving nearly 1000 patients in total have shown that darbepoetin alfa decreases the number of transfused patients by 17-25% in absolute terms, and that it probably reduces fatigue. However, one-quarter of patients receiving darbepoetin were nonetheless transfused. (4) In the absence of reliable comparisons, there is no firm evidence that darbepoetin alfa is more effective than other epoetins. (5) According to relatively imprecise company reports, darbepoetin alfa increased the risk of thromboembolic events during clinical trials (6% versus 3%), including pulmonary embolism (1.3% versus 0%); the company also states that darbepoetin alfa does not increase the risk of arterial hypertension, a classical effect of epoetin that is mentioned in the summary of product characteristics (SPC). Placebo-controlled trials and dose-finding studies show no impact on the outcome of cancer, but follow-up is limited and a negative effect cannot be ruled out. The company states that no cases of erythroblastopenia have occurred among more than 70 000 treated patients. (6) According to the SPC, darbepoetin alfa can be given once a week. However, the optimal epoetin dosing schedule is unknown. Epoetin therapy takes several weeks to correct anaemia, whereas transfusion is immediately effective. (7) In practice, darbepoetin alfa seems a little easier to administer than epoetin alfa or beta, but the advantages and disadvantages of these drugs as compared with blood transfusion are not entirely clear.
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PMID:Darbepoetin alfa: new indication/new dosage. No proven advantage in chemotherapy-induced anaemia. 1628 72

Patients with cancer receiving chemotherapy often have chemotherapy-induced anemia (CIA) and reduced quality of life. Darbepoetin alfa can effectively treat CIA when administered at an extended dosing interval of once every 3 weeks (Q3W). Darbepoetin alfa administered Q3W may allow synchronization of darbepoetin alfa therapy with chemotherapy administered Q3W. This multicenter, open-label, 16-week study evaluated the effectiveness and safety of darbepoetin alfa administered as a fixed dose (300 mug) Q3W in patients with CIA. Eligible patients (> or =18 years) were anemic (hemoglobin <11g/dl), had a nonmyeloid malignancy, and were receiving multicycle chemotherapy. This analysis includes 1,493 patients who received at least one dose of darbepoetin alfa. The effect of baseline hemoglobin (<10 or > or =10 g/dl) on clinical outcomes was evaluated. Patients in the > or =10-g/dl stratum achieved the hemoglobin target range (11-13 g/dl)in less time than patients in the <10-g/dlstratum (3 weeks vs. 9 weeks). More patients in the > or =10-g/dl stratum achieved the hemoglobin target range (87% vs. 66%); however, similar proportions of patients in both strata maintained hemoglobin within the target range (73% vs. 71%). Fewer patients in the > or =10-g/dl stratum received RBC transfusions from week 5 to the end of the study (12% vs. 28%). Over 50% of patients in both strata reported clinically significant improvements (> or =3-point increase) in Functional Assessment of Cancer Therapy-Fatigue score. Twenty-eight percent of patients reported serious adverse events; 3% of all patients had a venous or arterial thrombotic event. This study demonstrates that darbepoetin alfa Q3W is well tolerated and effective for treating CIA.
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PMID:Darbepoetin alfa administered every three weeks is effective for the treatment of chemotherapy-induced anemia. 1661 37


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