Treatment of cancer-related anemia with epoetin alfa: a review
Erminia FerrarioLeonardo FerrariPaolo BidoliDaniela De CandisMichele Del VecchioSara De DossoRoberto BuzzoniEmilio Bajetta
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Epoetin alfa
New patients starting dialysis typically have hemoglobin (Hb) and hematocrit (Hct) levels well below the target range of 11 to 12 g/dL (33% to 36%) recommended by the NKF-K/DOQI. Despite the emphasis on anemia as a quality indicator, low Hb levels often persist for months after dialysis is initiated. Several factors can help promote timely correction of anemia. (a) proactively assessing anemia-related laboratory indicators, (b) calculating weight-based Epoetin alfa starting doses, (c) starting Epoetin alfa therapy on the first day of dialysis for all eligible patients, and (d) proactively assessing patients for conditions that may affect the erythropoietic response. Through proactive, protocol-mandated interventions, nurses can help ensure that anemia is corrected promptly.
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Erythropoietin and its receptor function as primary mediators of the normal physiological response to hypoxia. Erythropoietin is recognized for its central role in erythropoiesis, but studies in which recombinant human erythropoietin (epoetin alfa) is injected directly into ischaemic rodent brain show that erythropoietin also mediates neuroprotection. Abundant expression of the erythropoietin receptor has been observed at brain capillaries, which could provide a route for circulating erythropoietin to enter the brain. In confirmation of this hypothesis, systemic administration of epoetin alfa before or up to 6 h after focal brain ischaemia reduced injury by 50–75%. Epoetin alfa also limited the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis and excitotoxicity induced by kainate. Thus, systemically administered epoetin alfa in animal models has neuroprotective effects, demonstrating its potential use after brain injury, trauma and multiple sclerosis. It is evident that erythropoietin has biological activities in addition to increasing red cell mass. Given the excellent safety profile of epoetin alfa, clinical trials evaluating systemically administered epoetin alfa as a general neuroprotective treatment are warranted.
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Recombinant human erythropoietin (r-HuEPO; epoetin alfa) is well established as safe and effective for the treatment of anemia. In addition to the erythropoietic effects of endogenous erythropoietin (EPO), recent evidence suggests that it may elicit a neuroprotective effect in the central nervous system (CNS). Preclinical studies have demonstrated the presence of EPO receptors in the brain that are up-regulated under hypoxic or ischemic conditions. Intracerebral and systemic administration of epoetin alfa have been demonstrated to elicit marked neuroprotective effects in multiple preclinical models of CNS disorders. Epoetin alfa has also been shown to prevent the loss of autoregulation of cerebral blood flow in a model of subarachnoid hemorrhage. The mechanisms of EPO-induced neuroprotection include prevention of glutamate-induced toxicity, inhibition of apoptosis, anti-inflammatory effects, antioxidant effects, and stimulation of angiogenesis. Collectively, these findings suggest that epoetin alfa may have potential therapeutic utility in patients with ischemic CNS injury.
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Goal: to examine the level of erythropoietin among patients with diabetes mellitus type 1 (DM 1) and different types of anemia and stages of diabetic nephropathy. Materials and methods: erythropoietin level analysis were conducted among 121 patients with DM 1 with and without anemia. Results: patients suffering from DM type 1 with anemia for less than 5 years have higher erythropoietin rates, than those who have DM for 5-15 years and longer time. Patients who suffer from DM for more than 15 years have the same erythropoietin rates regardless of the fact if they also have anemia or not. DM patients with anemia experience the decrease of erythropoietin level as far as Chronic Kidney Disease (CKD) is progressing. This decrease becomes statistically significant among patients with CKD of the 3, 4, and 5 stages (in comparison with patients without diabetic nephropathy (p=0,00)). Patients with Anemia Chronic Disease (ACD) and CKD have the same erythropoietin rates as patients without anemia (p=0,93 and p=0,40). Conclusion: The longer patients suffer from DM 1 and the CKD progress, the more the level of erythropoietin is going down. At duration DM 1 more than 15 years level of erythropoietin at patients DM with anemia corresponds to level of erythropoietin at patients without anemia. Patients with ACD don't have correlation of level of hemoglobin with erythropoietin. Where there is ACD, no hemoglobin-related increase in erythropoietin level is observed (which can be the reason of its appearance and advance). Patients with iron deficiency anemia, have elevating the level of erythropoietin despite an appreciable lesion of function of kidneys.
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OBJECTIVE To identify and treat a unique form of anemia in patients with long-term IDDM. RESEARCH DESIGN AND METHODS Patients with IDDM, unexplained symptomatic anemia, and serum creatinine levels of < 177 μmol/l (2.0 mg/dl) were treated with epoetin alfa (Procrit, Ortho Biotech, Raritan, NJ), 50 U/kg three times weekly, subcutaneously, to reach a target hematocrit of 38–40%. Baseline serum erythropoietin titers were measured before drug therapy. RESULTS Six patients were treated with epoetin alfa. Median age of the group was 74 years, with IDDM being diagnosed for a median of > 20 years. All patients had symptoms of anemia with a median hematocrit of 28.9% (range 27–31). Compared with iron deficiency control patients, the group had a limited erythropoietin (EPO) response to the degree of anemia. All patients showed increases in hematocrit, median peak of 40.9%, with median time-to-peak response of 12 weeks. Baseline symptoms of anemia resolved in all patients. No adverse effects were noted during the treatment period. CONCLUSIONS There is a unique form of anemia in patients with long-term IDDM and clinically normal renal function who respond to low-dose epoetin alfa therapy. The rapid response to therapy and depressed baseline erythropoietin titers suggest the anemia is due to a lack of endogenous EPO release.
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Hematology
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End-stage renal disease (ESRD) typically is associated with severe anemia. The major contributor to the anemia appears to be the absolute or relative deficiency of erythropoietin (EPO) production by the kidney. A series of clinical trials have been conducted in the United States using recombinant human EPO (rh EPO) to treat anemic patients with ESRD. The encouraging results of the Phase I-II clinical trials have been confirmed in a multicenter trial in which over 250 patients have been treated. The results indicate that rh EPO can effectively correct the anemia of ESRD and the rate of correction is dependent upon the initial dose given. The rHuEpo was well tolerated, produced few or no direct side effects, and was effective in greater than 95 percent of the patients. rh EPO should have a major role in the correction of the anemia of ESRD and contribute significantly to the rehabilitation of such patients.
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As the antitumor activity of radiation is mediated via its interaction with oxygen to form labile free radicals, the intratumoral oxygen level has an important influence on the ability of radiation therapy to kill malignant cells. By decreasing the oxygen-carrying capacity of the blood, anemia may result in tumor hypoxia and may have a negative influence on the outcome of radiotherapy for various malignancies, even for small tumors not normally assumed to be hypoxic. In addition, anemia also has a negative effect on the quality of life of cancer patients, as evidenced by worsening fatigue. As a high proportion (about 50%) of cancer patients undergoing radiotherapy are anemic prior to or during treatment, strategies to correct anemia and/or the resultant tumor hypoxia are increasingly being considered an important component of treatment. In particular, epoetin alfa (recombinant human erythropoietin), which has proved an effective and well-tolerated means of raising hemoglobin levels in anemic patients receiving radiotherapy, potentially could reverse the negative prognostic influence of a low hemoglobin in patients with certain malignancies. Radiation oncologists need to be aware of the possibility of anemia in cancer patients undergoing radiotherapy so that timely intervention can be instituted whenever anemia is diagnosed.
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Abstract: Objective: To study the outcome of high dose erythropoietin (EPO) therapy in the elderly with the unexplained anemia Patients and Methods: The 60-year old or older participants with the unexplained anemia are treated with weekly subcutaneous injection of erythropoietin (EPO), seven with 30,000 units of beta-EPO (Recormon®) and one with 40,000 units of alpha-EPO (Eprex®). Results: There are eight patients with mean age of 72.4 + 8.2 years. Every case has complete recovery within 4-16 weeks, mean of hemoglobin level is raised from 9.9 + 0.6 g% to 13.2 + 0.6 g%. Four from seven (57.1%) participants of Recormon group respond well within the first four weeks. No side effect or complication is detected. Conclusion: High dose EPO can correct the unexplained anemia in all elderly people within 4-16 weeks. Key words: Erythropoietin, Unexplained Anemia of the Elderly บทคดยอ วตถประสงค : ศกษาผลการรกษาภาวะโลหตจางไมทราบสาเหตในผสงอายดวย erythropoietin (EPO) ความเขมขนสง ผปวยและวธการ : ผปวยอายมากกวา 60 ป ทมภาวะโลหตจางไมทราบสาเหตไดรบการรกษาดวยการฉด EPO เขาใตผวหนง โดย 7 ราย ฉดดวย beta-EPO (Recormon®) 30,000 หนวย อก 1 ราย ฉดดวย alpha-EPO (Eprex®) 40,000 หนวย ทกสปดาห ผลการศกษา : ผปวยทง 8 ราย อายเฉลย 72.4 + 8.2 ป ทกรายหายจากภาวะโลหตจางภายใน 4-16 สปดาห, ระดบ hemoglobin เฉลยเพมจาก 9.9 + 0.6 g% เปน 13.2 + 0.6 g% โดยผปวย 4 ใน 7 รายจากกลม Recormon (รอยละ 57.1) หายภายใน 4 สปดาหแรกของการรกษา ไมพบผลขางเคยง หรอภาวะแทรกซอนใด ๆ สรป : EPO ขนาดสงทำใหผสงอายทมโลหตจางไมทราบสาเหตทกรายหายได ภายใน 4-16 สปดาห คำสำคญ : erythropoietin, ภาวะโลหตจางไมทราบสาเหตในผสงอาย
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