Correlation between variation in quality of life and change in hemoglobin level after treatment with epoetin alfa 40,000 IU administered once-weekly

Introduction Anemia is frequently associated with cancer due to the disease itself and antineoplastic treatments. This open-label, uncontrolled, multi-center study evaluated the effects of once-weekly (qw) epoetin alfa 40,000 IU on hemoglobin (Hb) levels and quality of life (QoL) in anemic patients receiving chemotherapy for solid tumors. Materials and methods A total of 522 patients with Hb level ≤12 g/dL received epoetin alfa 40,000 IU qw subcutaneously for 9–20 weeks to reach and maintain Hb range of 12–14 g/dL. QoL was assessed with the Functional Assessment of Cancer Therapy-Anemia (FACT-An [anemia sub-scale]) and Cancer Linear Analogue Scale (CLAS) at study entry, after two chemotherapy cycles, and at study end. Results Mean baseline Hb was 10.43 g/dL. Hb increases (g/dL) from baseline after 4, 8, 12 weeks and at study end were 1.07, 1.77, 1.92 and 1.71 g/dL, respectively. Response rates (Hb increase ≥1 and ≥2 g/dL during trial) were 81% and 61%, respectively. Mean increases in the FACT-An score from baseline (mean 55.4) were 3.1 after two chemotherapy cycles and 3.3 at study end; mean increases in the CLAS score from baseline (58.4 mm) were 5.9 mm after two chemotherapy cycles and 6.5 mm at study end. Discussion The greatest QoL increase was recorded when patients approached Hb level of 12 g/dL, independent of the baseline Hb level. Hb changes from baseline to trial end were related to corresponding changes in the FACT-An score. A positive correlation was also observed in patients with progressive disease. Adverse events were essentially those associated with chemotherapy. Incidence of thrombovascular events (6.7%) did not differ from the expected standard treatment in cancer patients. Epoetin alfa 40,000 IU qw increased Hb levels and improved or preserved QoL.     

Epoetin alfa in cancer patients: evidence-based guidelines.

Anemia is a common cause of cancer-related fatigue. A systematic review of the literature was performed to establish guidelines on the use of epoetin alfa for the treatment of anemia. The evidence in support of these guidelines was selected, reviewed, and summarized by the members of the Canadian Cancer and Anemia Guidelines Development Group. The effects of epoetin alfa on quality of life (QOL) in patients with cancer were examined in 5 randomized, placebo-controlled trials and 2 large, open-label, nonrandomized, community-based studies. The effects of epoetin alfa on red blood cell transfusion requirements were examined in 19 randomized controlled trials (RCTs) with 21 comparisons. All trials compared epoetin alfa to a suitable control group, examined specified outcome measures that could be analyzed, and studied patients with cancer who were receiving chemotherapy. Trials involving patients with hematologic malignancies originating in the bone marrow were excluded. Outcome measures included 1) quality of life (QOL) (as measured by scales including the Linear Analogue Self-Assessment [LASA] and the Functional Assessment of Cancer Therapy [FACT] subscales), and 2) transfusion requirements (as measured by the proportion of patients requiring transfusion and amount of transfusion). The analysis confirmed that epoetin alfa produced statistically significant and clinically relevant improvements in QOL in patients with cancer. The overall relative risk ratio for transfusion among patients receiving epoetin alfa was calculated to be 0.60 (95% Cl, 0.53-0.69; P < 0.00001), representing a 40% reduction in the proportion of patients requiring transfusion. These results support recommendations for the use of epoetin alfa in patients with cancer-related anemia.     

Pharmacokinetics and pharmacodynamics of once-weekly subcutaneous epoetin alfa in critically ill patients: results of a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Medical, surgical, or mixed medical/surgical intensive care units. PATIENTS: A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%. INTERVENTIONS: Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n=48) or matching placebo (n=25) for up to 4 wks. MEASUREMENTS AND MAIN RESULTS: Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo. CONCLUSION: Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.     

Use of epoetin alfa in critically ill patients

OBJECTIVE: To discuss the controversies regarding the use of epoetin alfa (EPO) for reducing red blood cell (RBC) transfusions in critically ill patients with anemia. DATA SOURCES: A MEDLINE search (1966-July 2003) was conducted using the search terms anemia; critical illness; erythropoietin; epoetin alfa; and erythropoietin, recombinant. References of selected articles were reviewed for studies that may have been missed by the computerized search. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of EPO for anemia of critical illness with an emphasis on data obtained from controlled trials. DATA SYNTHESIS: Anemia is a common complication in patients admitted to the intensive care unit (ICU). Two prospective, randomized studies have demonstrated decreased transfusion requirements associated with EPO administration in medical/surgical patients who were in the ICU for at least 3 days and had hematocrit concentrations <38%. No differences were found in length of stay or mortality. A multicenter trial found that a restrictive strategy of RBC transfusion (hemoglobin goal 7-9 g/dL) was associated with in-hospital mortality lower than that with a more liberal approach, which calls into question the 38% hematocrit goal in the EPO trials. Furthermore, preliminary results from an economic analysis of EPO use in the ICU setting have demonstrated that EPO is not cost-effective. CONCLUSIONS: Given the controversies surrounding EPO administration in critically ill patients, institutions are encouraged to develop EPO guidelines to help ensure the most appropriate use of this expensive product. Additional studies regarding patients most likely to benefit from EPO therapy, the most effective dosing regimen, and use of adjunctive therapies are needed.     

Effects of blood transfusion on clinical and functional outcomes in patients with hip fracture

BACKGROUND: Anemia and transfusion are common among elderly patients requiring surgery. The effects of transfusion on morbidity and mortality are controversial. The influence of transfusion on risk-adjusted mortality, readmissions, and functional mobility was examined. STUDY DESIGN AND METHODS: A consecutive cohort of 551 patients undergoing surgery for hip fracture at four hospitals was prospectively studied. Outcomes were death, readmission, and functional independence measure-locomotion scores within 60 days of discharge. The trigger Hb level was defined as the lowest value before the first postoperative transfusion. Multivariate analyses adjusted for a validated, hip-fracture-specific risk model and predictors of transfusion. RESULTS: Overall, 54.4 percent of patients received transfusions after surgery. Seventy-two percent of patients with a lowest postoperative Hb level of less than 10.0 g per dL received transfusions compared to 19.6 percent of those whose lowest measurement was at least 10.0 g per dL (p < 0.0001). In the 60 days after discharge, 3.8 percent of patients died and 16.9 percent were readmitted. Transfusion was associated with lower risk-adjusted odds of readmission (OR, 0.54; 95% CI, 0.30-0.97), but it did not influence mortality or mobility functioning. In subgroups analyses, the benefit of transfusion on readmission rates appeared to be concentrated among patients with a trigger Hb level of less than 10.0 g per dL. For patients with a trigger Hb level of at least 10.0 g per dL, transfusion did not affect risk-adjusted rates of death or readmission, but was associated with better risk-adjusted functional mobility scores (p < 0.01). CONCLUSIONS: Postoperative transfusion reduced the risk of readmission but did not decrease mortality or improve mobility. Randomized controlled trials of different transfusion strategies will be needed to clarify the true benefits and risks of transfusion in surgical patients.     

The effectiveness and tolerability of epoetin alfa in patients with multiple myeloma refractory to chemotherapy

Anemia is a frequent complication of multiple myeloma, becoming chronic in patients who are resistant to chemotherapy. This randomized, parallel, controlled multicenter study (71 patients receiving concomitant chemotherapy) evaluated the efficacy and safety of epoetin alfa in improving anemia and eliminating the need for transfusions in multiple myeloma patients refractory to conventional first- or second-line chemotherapy. Forty patients were treated with subcutaneous epoetin alfa (150 IU/kg per dose, increasing to 300 IU/kg per dose, every 3 weeks) for 6 months, and 31 entered a control group. The epoetin alfa group had a significantly (P≤0.001) greater percentage of patients (75% vs. 21%) with increases in hemoglobin levels and/or reduced transfusion requirements. In 44 non pre-transfused patients (20 controls, 24 in the epoetin alfa group), the mean increase in hemoglobin was significantly (P≤0.0001) greater in the epoetin alfa group (+2.1 vs. −0.2 g/dl). Increases in hematocrit and red blood cells were also significantly (P≤0.0001) greater in epoetin alfa-treated patients, with corresponding reductions in transfusion requirement. In the 27 pre-transfused patients (11 controls, 16 in the epoetin alfa group), there was a trend towards reduced transfusional need in epoetin alfa-treated patients. Thus, in patients with multiple myeloma refractory to chemotherapy epoetin alfa is a well-tolerated treatment which improves anemia in non pre-transfused patients and appears to reduce transfusion need in those previously transfused.     

Is there a place for epoetin alfa in managing anemia during critical illness?

BACKGROUND: Anemia is a common problem in critically ill patients. As a result, blood transfusions are often used in the intensive care unit (ICU) setting. However, mounting evidence shows that blood transfusions may contribute to negative outcomes, such as transfusion-related infections, organ dysfunction, and immunosuppression. Supplementation with epoetin alfa is currently used in some medical centers to manage anemia in critically ill patients. OBJECTIVE: This review discusses the risks with blood transfusions and the clinical evidence supporting the use of epoetin alfa in managing edema during critical illness. METHODS: A search was conducted in MEDLINE and Current Contents (1966-2003) using the terms epoetin alfa, recombinant human erythropoietin, and anemia. Articles addressing anemia and the use of epoetin alfa in critically ill patients were selected and assessed. From this selection, the cited references addressing the etiology of anemia in the ICU and the risks associated with blood transfusions were manually extracted and reviewed. RESULTS: Several reports have shown that critically ill patients display evidence of anemia due to a blunted erythropoietin response. One large, randomized, placebo-controlled study assessed the effect of SC epoetin alfa on blood transfusions in the ICU. In this study, 40, 000 IU administered weekly for up to 4 weeks resulted in an overall transfusion reduction (9.9% absolute risk reduction; P<0.001 ). Other, smaller studies using different dosing regimens in critically ill patients have also demonstrated that epoetin alfa can decrease the need for transfusion. CONCLUSION: The use of epoetin alfa in critically ill patients can decrease the number of blood transfusions required during hospitalization, and potentially result in transfusion avoidance. Because of the scarce amount of evidence and the diversity of dosing regimens used used, no strict recommendations can be drawn from this review.     

Effects of anemia and blood transfusion in acute myocardial infarction in rats

BACKGROUND: The optimal hemoglobin (Hb) level in acute myocardial infarction (MI) is unknown. The goal of this study was to determine the optimal Hb concentration in acute MI and whether transfusion of fresh blood to correct anemia reduces myocardial injury and improves outcome.
STUDY DESIGN AND METHODS: Anemia was induced in rats by an iron-deficient diet and phlebotomy. MI was induced by left coronary artery ligation. Some rats received transfusion of fresh blood. Survival, hemodynamic measurements, and infarct size were determined 24 hours after MI.
RESULTS: Reduction of Hb to 80 to 90 and 70 to 80 g/L decreased 24-hour survival after MI to 42 and 47%, respectively (p < 0.05). Infarct size was increased in both 70 to 80 and 80 to 90 g/L anemic groups compared to the normal Hb group (p < 0.05). Cardiac function was decreased in anemic groups after MI (p < 0.01). Transfusion of fresh blood to increase Hb from 80 to 90 g/L to 100 g/L decreased infarct size (p < 0.05) and improved cardiac function (p < 0.05), and a trend toward better survival (73%) was observed. Transfusion from 80 to 90 g/L Hb to 120 g/L Hb was associated with larger infarct size (p < 0.05), decreased cardiac function (p < 0.05), and no improvement in survival (47%, p = NS).
CONCLUSION: Anemia increases infarct size and decreases cardiac function and survival in acute MI. Transfusion of anemic animals up to 100 g/L Hb with fresh blood reduces infarct size and improves cardiac function. However, transfusion to 120 g/L Hb did not demonstrate any additional benefit and was associated with larger infarcts.     

Treatment of anemia in patients with HIV infection, Part 1: The need for adequate guidelines.

Anemia in HIV-infected individuals, still a common hematologic complication in the highly active antiretroviral therapy (HAART) era, is associated with shortened survival, increases in the rate of disease progression, and reduction in quality of life. Based on a thorough review of the literature, guidelines were developed for the assessment, diagnosis, monitoring, and treatment of anemia in patients with HIV/AIDS by a consensus committee consisting of nurses from academia and clinical practice. A major goal of this committee is to increase awareness within the nursing community of the prevalence of anemia in HIV-infected patients and its impact on their lives. Anemia developed in close to 90% of HIV-infected patients before the introduction of HAART, and it is still found in up to 46% of patients in the HAART era. Another goal is to encourage screening for anemia and the adaptation of a proposed classification system of anemia based on a graded decrease in hemoglobin levels.     

Response of erythropoiesis and iron metabolism to recombinant human erythropoietin in intensive care unit patients

OBJECTIVES: Critically ill patients often are anemic, which may impair oxygen delivery. Transfusion of red cells and supplementation with vitamins or iron are the usual therapeutic strategies, whereas only sporadic data are available on the use of epoetin alfa in these patients. We investigated endogenous erythropoietin (EPO) production and the response to epoetin alfa in anemic intensive care unit (ICU) patients. DESIGN: Randomized, open trial. SETTING: Multidisciplinary ICU in a single secondary care center. PATIENTS: Thirty-six critically ill patients admitted to the ICU who became anemic (hemoglobin concentration, <11.2 g/dL or <12.1 g/dL in case of cardiac disease) were randomized to one of three study groups. INTERVENTIONS: All patients received folic acid (1 mg) daily. The control group received no additional therapy, the iron group received 20 mg of iron saccharate intravenously (iv) daily for 14 days. The EPO group received iv iron and epoetin alfa (300 IU/kg) subcutaneously on days 1, 3, 5, 7, and 9. MEASUREMENTS AND MAIN RESULTS: Blood and reticulocyte counts were measured daily for 22 days. Serum EPO, C-reactive protein, serum transferrin receptor, and iron variables were measured on days 0, 2, 6, 10, and 21. Blood loss and red cell transfusions were recorded. Serum EPO concentrations were inappropriately low for the degree of anemia at baseline, with no difference between patients with and without renal failure. Exogenous administration of EPO increased EPO concentrations from 23+/-13 to a maximum of 166+/-98 units/L on day 10 (p < .05). Reticulocyte count increased exclusively in the EPO group from 56+/-33 x 10(9)/L to a maximum of 189+/-97 on day 13 (p < .05). Serum transferrin receptor rose only in the EPO group from 3.7+/-1.4 to 8.6+/-3.1 mg/L on day 10 (p < .05) and remained elevated on day 21, indicating an increase in erythropoiesis. Hemoglobin concentration and platelet count remained identical in the three study groups. CONCLUSION: Endogenous EPO concentrations are low in critically ill patients. The bone marrow of these patients is able to respond to exogenous epoetin alfa, as shown by elevated concentrations of reticulocytes and serum transferrin receptors.     

The influence of baseline hemoglobin concentration on tolerance of anemia in cardiac surgery

BACKGROUND: Current red blood cell (RBC) transfusion guidelines assume that most acutely anemic patients can tolerate hemoglobin (Hb) concentrations as low as 6.0 to 7.0 g per dL and recommend that range as the transfusion threshold in patients who have no overt signs of organ dysfunction. Nonetheless, "normal" Hb concentrations vary widely in the population, and this variability may influence patients' tolerance of acute anemia. This retrospective cohort study was carried out to test this hypothesis. STUDY DESIGN AND METHODS: Data were analyzed on 10,179 consecutive patients who had normal Hb concentrations (12.0-16.0 g/dL in women and 13.0-18.0 g/dL in men) and underwent on-pump cardiac surgery from 1999 to 2006 at an academic hospital. The relationships of lowest intraoperative Hb concentration and maximum decrease in Hb concentration (from baseline) with the composite outcome of in-hospital death, stroke, or kidney failure were determined in various patient subgroups. RESULTS: The relationship between lowest Hb concentration and adverse outcomes was not independently associated with increased risk. In contrast, the relationship between maximum decrease in Hb concentration and adverse outcomes was independently associated with increased risk, with a 50 percent decrease being the threshold beyond which risk was increased (adjusted odds ratio, 1.53; 95% confidence interval, 1.12-2.08; p = 0.007). CONCLUSION: The degree of acute anemia that patients can safely tolerate during cardiac surgery is inversely related to their baseline Hb concentration. Current transfusion guidelines do not account for this relationship.     

Speed of haemoglobin response in patients with cancer: a review of the erythropoietic proteins

Background Patients with cancer-related anaemia generally have a poor prognosis. Evidence suggests that an effective erythropoietic protein (epoetin)-mediated haemoglobin (Hb) response provides marked improvement in quality of life (QoL). An early Hb response to erythropoietic protein therapy in these patients would appear ideal but few studies have compared the speed of response to different erythropoietic proteins, or the potential benefits associated with an early Hb response. Results and discussion The pharmacokinetic/pharmacodynamic profiles of commercially available erythropoietic proteins are reviewed along with available clinical data to examine Hb response and associated clinical outcomes for each of these agents. Randomised, head-to-head trials comparing epoetin alfa and darbepoetin alfa suggest that patients administered with epoetin alfa achieve a satisfactory Hb response significantly earlier than those given darbepoetin alfa, and with consistently lower monthly transfusion rates. Non-comparative studies support this, suggesting also that epoetin beta may provide a relatively faster Hb response in a greater number of patients than either epoetin alfa or darbepoetin alfa, irrespective of malignancy or chemotherapy type. Moreover, studies suggest consistently that a ‘front-loading’ dosing regimen with epoetin alfa does not convey improved speed of Hb response over epoetin beta administered according to current clinical practice guidelines. Conclusions Given the poor prognosis of anaemic patients with cancer, the use of an agent which provides clinical benefits quickly but with minimal thromboembolic risk, should be considered an essential component of anaemia management in these patients. However, more head-to-head studies are required to confirm the relative efficacy of currently available erythropoietic proteins.     

A multicenter retrospective cohort study of practice patterns and clinical outcomes of the use of darbepoetin alfa and epoetin alfa for chemotherapy-induced anemia

BACKGROUND: Darbepoetin alfa is the second erythropoietic protein to be approved for the treatment of chemotherapy-induced anemia (CIA). In the clinical setting, darbepoetin alfa can be administered less frequently than epoetin alfa with similar efficacy. Practice patterns and outcomes associated with the use of darbepoetin alfa and epoetin alfa in the clinical setting have not been reported. OBJECTIVE: This study compared practice patterns and clinical outcomes of the use of darbepoetin alfa and epoetin alfa for CIA at oncology practices in the United States. METHODS: This was a multicenter retrospective cohort study. Data were abstracted from the medical charts of consecutive patients who began darbepoetin alfa treatment between August 1 and October 4, 2002, or epoetin alfa treatment between April 1 and July 31, 2002, and were receiving concurrent chemotherapy. These data were used to determine the initial dose and dosing schedule, dose changes, and changes in hemoglobin concentrations after 4, 8, and 12 weeks of treatment, adjusted for red blood cell (RBC) transfusions, and the incidence of RBC transfusions over time. To minimize potential bias, the study protocol defined specific end points and prespecified analytic techniques for assessing clinical outcomes with the 2 agents. RESULTS: The records of 1391 patients from 16 community and hospital outpatient oncology clinics were abstracted. Of these, 1293 patients (93.0%) received only 1 erythropoietic agent (darbepoetin alfa, 735 [56.8%]; epoetin alfa, 558 [43.2%]); the remainder received both agents. In the patients who received darbepoetin alfa, most (553 [75.2%]) received an initial dosage of 200 microg q2wk. A similar proportion (414 [74.2%]) received epoetin alfa at an initial dosage of 40,000 U qwk. As these were the regimens for the majority of patients whose records were abstracted, the results reported here are for these patients. The dose was increased in 63 darbepoetin alfa recipients (11.4%) and 58 epoetin alfa recipients (14.0%) at a median of 7 weeks. After 12 weeks, the 2 groups had an identical mean imputed change from baseline in hemoglobin concentration (1.0 g/dL), and the incidence of RBC transfusions during treatment was also similar between groups (darbepoetin alfa, 44553 [8.0%]; epoetin alfa, 39414 [9.4%]). CONCLUSIONS: Darbepoetin alfa 200 microg q2wk was used as a standard regimen for CIA at the 16 US oncology practices participating in this study. It appeared to be as effective as epoetin alfa 40,000 U qwk, with a reduced frequency of dosing.     

Role of oral versus IV iron supplementation in the erythropoietic response to rHuEPO: a randomized, placebo-controlled trial

BACKGROUND: Preoperative treatment with rHuEPO (epoetin alfa: EPREX, Janssen-Cilag; or PROCRIT, Ortho Biotech) in conjunction with iron supplementation increases the erythropoietic response in elective orthopedic surgery patients, but it is not known whether the magnitude of this response is dependent on the route of iron administration. STUDY DESIGN and METHODS: Non-iron-deficient patients undergoing elective orthopedic surgery (N = 110) with baseline Hb > or =10 to < or =13 g per dL were randomly assigned to receive either epoetin alfa (600 IU/kg) plus IV iron (n = 29) or oral iron (n = 29) or placebo plus IV iron (n = 25) or oral iron (n = 27) in this 14-day study. RBC production, Hb, Hct, reticulocytes, iron status, and adverse events were monitored throughout the study. RESULTS: Epoetin alfa treatment plus either oral or IV iron supplementation significantly increased total RBC production, Hb, Hct, and reticulocytes over the values seen with the respective placebo treatments (p = 0.0001). There were no differences between the epoetin alfa treatment groups. Placebo treatment plus oral or IV iron supplementation was not associated with increases in hematologic values. There were no differences in the incidence of adverse events among the treatment groups. CONCLUSION: There was a comparable erythropoietic response to epoetin alfa, irrespective of the route of iron administration. The route of iron administration, therefore, does not modulate the erythropoietic response to epoetin alfa in patients who are not iron deficient. Safety and convenience benefits may be gained by adopting oral iron supplementation in this patient subset.     

Effect of darbepoetin alfa administered once monthly on maintaining hemoglobin levels in older patients with chronic kidney disease

Background: The anemia of chronic kidney disease (CKD) is associated with increased hospitalizations, increased cardiovascular morbidity and mortality, and diminished quality of life in the elderly. Darbepoetin alfa is an erythropoiesis-stimulating agent that has been shown to be effective in treating anemia in patients with CKD (but not on dialysis) when administered using extended-dosing regimens.Objective: The purpose of this post hoc analysis was to examine the efficacy and safety profile of once-monthly (QM) darbepoetin alfa in study patients stratified according to age (ie, <65, 65–74, and ≥75 years).Methods: Patients with CKD but not on dialysis, receiving darbepoetin alfa every other week (Q2W), and with stable hemoglobin (Hb) levels between 11 and 13 g/dL, inclusive, were enrolled in this 33-week, multicenter, open-label, single-arm study. The study was carried out at 36 US centers and consisted of a 24-week QM darbepoetin alfa dose-titration period followed by an 8-week evaluation period. Hb levels were measured Q2W. Study results were stratified according to patient age (<65, 65–74, and ≥75 years).Results: A total of 152 patients (79 women, 73 men) were enrolled; 55 patients (36%) were <65 years of age, 46 (30%) were 65 to 74 years of age, and 51 (34%) were ≥75 years of age. In patients who received ≥1 dose of darbepoetin alfa, Hb levels ≥11 g/dL were maintained in 76%, 80%, and 71% of patients aged <65, 65 to 74, and ≥75 years, respectively. For patients who completed the study, the proportions who maintained Hb levels ≥11 g/dL were 83%, 88%, and 85%, respectively, for the 3 age groups. The safety profile of QM darbepoetin alfa in this study was consistent with that expected in patients with CKD not receiving dialysis.Conclusions: Darbepoetin alfa administered QM maintained Hb levels ≥11 g/dL in patients with CKD (not on dialysis) aged <65, 65 to 74, and ≥75 years. This treatment regimen may help optimize anemia management for older community-dwelling and long-term care patients.     

Dosing intervals and hemoglobin control in patients with chronic kidney disease and anemia treated with epoetin alfa or darbepoetin alfa: a retrospective cohort study

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD). The approved dosing interval for currently available erythropoiesis-stimulating agents (ESAs) is 2 to 3 times weekly for epoetin alfa (EPO) and every 1 to 2 weeks for darbepoetin alfa (DARB). However, clinicians sometimes use less frequent dosing in the interest of convenience. OBJECTIVES: This study investigated patterns of actual ESA use (doses and dosing intervals) and hemoglo- bin (Hb) control in adult outpatients with CKD not requiring dialysis at the Cleveland Clinic Foundation anemia clinic. The distribution of and variability in Hb levels in these patients were also examined. METHODS: The clinical charts and electronic records of adult outpatients with CKD who initiated ESA therapy before March 2005 were reviewed to identify the initial, dominant (used for the longest consecutive period), and final dosing intervals and mean weekly doses of EPO and DARB. Hb control was examined in terms of maximum deviations >12 g/dL and <11 g/dL, and the proportions of measurements outside these values. RESULTS: The analysis included data from 111 outpatients (mean [SD] age, 65.9 [14.4] years; 53.2% male; 66.7% white, 29.7% black, 2.7% other, 0.9% unknown ethnicity). Twenty-one patients received EPO only, 74 received DARB only, and 16 switched ESAs. The mean duration of follow-up was 20.5 months. The most common initial dosing intervals were qwk for EPO (66.7%) and q2wk for DARB (90.5%). The dominant dosing intervals were q2wk in 61.9% of EPO patients and q3wk in 62.3% of DARB patients. However, 80.0% of those who received EPO q2wk and 63.2% of those who received DARB q3wk eventually returned to their initial dosing intervals. The largest proportions of Hb mea- surements <11 g/dL occurred at dominant dosing intervals of qwk for EPO and q2wk for DARB (both, 46.0%; 11 and 26 patients, respectively), whereas the largest proportions of measurements >12 g/dL occurred with EPO dosed at q2wk (44.0%; 5 patients) and DARB dosed at >q4wk (62.0%; 5 patients). CONCLUSIONS: The patterns of ESA usage in adult outpatients with CKD at this center indicated that clinicians extended dosing intervals beyond those in the approved prescribing information. However, variations in Hb concentrations occurred during maintenance therapy administered at extended dosing intervals, resulting in the resumption of shorter dosing intervals in the majority of patients.     

Prophylactic recombinant epoetin alfa markedly reduces the need for blood transfusion in patients with metastatic melanoma treated with biochemotherapy

Treatment of metastatic melanoma with biochemotherapy results in the rapid onset of anemia, requiring blood transfusion in 9 of 13 (69%) patients. Prophylactic use of weekly subcutaneous recombinant epoetin alfa eliminated the need for transfusion in all but 1 of 21 (5%) patients.     

Consensus statement: anemia in HIV infection--current trends, treatment options, and practice strategies. Anemia in HIV Working Group

BACKGROUND: Despite important advances in antiretroviral therapy, anemia remains a problem in many HIV-infected patients. Although the incidence of anemia in these patients has decreased, its prevalence appears to have stabilized or decreased only slightly. Anemia has a deleterious effect on both functional capacity and quality of life, and has been associated with shortened survival. OBJECTIVE: The Anemia in HIV Working Group, an expert panel of physicians and researchers involved in the care of HIV-infected patients, met to determine the impact of anemia in this patient population; to develop practice strategies for the clinician treating HIV-infected patients with anemia; and to identify future research directions. METHODS: The proposed practice strategies are based on results of the available clinical trials (as identified through a MEDLINE search), a review of the literature, and the clinical experience and expert opinion of the panel. The present report is based on meetings held in February and June of 1998; as further experience with various treatment options accumulates and the impact of highly active antiretroviral therapy becomes clearer, the panel will reconvene to develop evidence-based guidelines. RESULTS: The working group considers HIV-associated anemia to be an important contributor to the morbidity and mortality of this infection. Recent reports indicate that recovery from anemia is associated with improved quality of life and survival. CONCLUSIONS: As HIV-infected persons live longer, maintaining quality of life becomes an increasingly important goal of treatment. When planning treatment strategies, clinicians should consider the quality-of-life decrement caused by anemia. Transfusions should be used when rapid recovery is required, and underlying conditions causing anemia should be treated, if possible. Recombinant human erythropoietin (rHuEPO) therapy is appropriate in certain HIV-infected persons and should be considered to maintain hemoglobin concentrations. The target hemoglobin level is 12 g/dL for men and 11 g/dL for women. Weekly rHuEPO dosing is suggested, initiated at 40,000 U, as has been established in patients with cancer.     

Anemia of cancer in intermediate-grade non-Hodgkin's lymphoma

BACKGROUND: Current literature suggests that anemia at baseline is an important adverse prognostic factor for lymphoma-related outcomes. We evaluated the prevalence, risk factors, and prognostic value of anemia in patients with intermediate-grade non-Hodgkin's lymphoma (IGNHL) treated in a community-based practice. METHODS: The retrospective sample included 591 patients who had IGNHL diagnosed between 1993 and 1999 and who were subsequently treated with CHOP chemotherapy. Anemia was defined as a hemoglobin (Hb) value < 12 g/dL. RESULTS: Anemia was present in 193 of 546 patients (35.3%). Baseline anemia was significantly associated with age > 60, extranodal sites > or = 2, Ann Arbor stage III or IV, elevated lactate dehydrogenase (LDH) level, B symptoms, and histology type. Baseline Hb was also a significant predictor of nonresponse to chemotherapy. CONCLUSIONS: Our study results support previous findings of a high prevalence of anemia in cancer patients before cytotoxic therapy and the adverse impact that baseline anemia has on response to chemotherapy.