Search

Purpose: Erythropoiesis-stimulating agents can reduce red blood cell transfusion rates in patients developing anemia while receiving chemotherapy. We investigated potential cost savings from reduced transfusion rates in patients starting darbepoetin alfa (DA) at higher versus lower hemoglobin (Hb) levels. Methods: Two systematic literature reviews were performed: transfusion outcomes in patients receiving DA stratified by baseline Hb level and costs of transfusion in Europe. Potential cost savings were calculated by multiplying the difference in transfusion rates between Hb levels by the midpoint of transfusion costs. Results: Despite differences in baseline characteristics, treatment duration and analysis technique, the clinical studies ( n = 8) showed that fewer transfusions were required when DA was initiated at higher versus lower Hb levels. The economic studies ( n = 9) showed that 1 unit of transfusion ranged from €130 to €537 (2010-adjusted values). Cost savings from initiating DA at higher versus lower Hb levels were €503-2,226 (2 units transfused) and €880-3,895 (3.5 units) per ten patients. Conclusions: Transfusion incidence increases with DA initiation at lower Hb levels. Potential cost savings depend on the number of units transfused and cost items included. DA initiation according to guidelines can reduce transfusions and potentially reduce transfusion-associated costs. [ABSTRACT FROM AUTHOR]

The erythropoiesis-stimulating agents (ESAs) erythropoietin and darbepoetin prevent transfusions among chemotherapy-associated anemia patients. Clinical trials, meta-analyses, and guidelines identify mortality, tumor progression, and venous thromboembolism (VTE) risks with ESA administration in this setting. Product labels advise against administering ESAs with potentially curative chemotherapy (United States) or to conduct risk-benefit assessments (Europe/Canada). Since 2007, fewer chemotherapy-associated anemia patients in the United States and Europe receive ESAs. ESAs and the erythropoietin receptor agonist peginesatide prevent transfusions among chronic kidney disease (CKD) patients; clinical trials, guidelines, and meta-analyses demonstrate myocardial infarction, stroke, VTE, or mortality risks with ESAs targeting high hemoglobin levels. U.S. labels recommend administering ESAs or peginesatide at doses sufficient to prevent transfusions among dialysis CKD patients. For dialysis CKD patients, Canadian and European labels recommend targeting hemoglobin levels of 10 to 12 g/dL and 11 to 12 g/dL, respectively, with ESAs. ESA utilization for dialysis CKD patients has decreased in the United States. [ABSTRACT FROM AUTHOR]

Erythropoiesis-stimulating agents (ESAs) are approved as an alternative to blood transfusions for treating anemia secondary to chemotherapy in patients with cancer. Recently, ESAs have been a source of controversy and confusion in the oncology community. This began when two European trials--the Breast Cancer Erythropoietin Survival Trial (BEST) and the Advanced Head-and-Neck Cancer Treated with Radiotherapy (ENHANCE) Study--raised safety concerns about decreased overall survival and increased venous thromboembolic events. In 2004, the United States Food and Drug Administration (FDA) convened its Oncologic Drugs Advisory Committee (ODAC) to review the data and reassess the risks and benefits of ESAs in patients with cancer. On May 10, 2007, ODAC reconvened when five trials (BEST, ENHANCE, AMG-20010103, AMG-20000161, and EPO-CAN-20) showed decreased overall survival. The briefing document noted that studies demonstrating detrimental effects on survival and/or tumor outcomes used an unapproved treatment regimen designed to maintain hemoglobin levels above 12 g/dl. On May 14, 2007, just days after the ODAC reconvened, the Centers for Medicare and Medicaid Services (CMS) released a proposed decision memo for a national coverage determination (NCD) imposing restrictions on ESAs. For health care providers, aspects of the proposed NCD were markedly inconsistent with FDA-approved ESA use and generally were considered ambiguous and unclear. Over objections of several professional associations and members of Congress, on July 30, 2007, CMS posted the final NCD and declared it effective immediately. When compared with FDA-approved labeling and professional society guidelines, the NCD revealed differences in ESA initiation, dosage escalation, dosage reduction, and definition of response. These discrepancies have generated confusion among health care providers, who are struggling over whether they can feasibly provide a dual system of care--one for Medicare patients and another for non-Medicare patients--that is evidence based. With this supplement, we hope to educate health care providers on the issues and challenges associated with policy-guided health care when discrepancies exist between the policy and evidence-based practice; offer guidance on implementing the NCD; and highlight the important role of pharmacists in the process. [ABSTRACT FROM AUTHOR]

Aim: While darbepoetin alfa (DA) can be administered once monthly (QM) to maintain haemoglobin (Hb) concentrations in anaemic patients with chronic kidney disease not on dialysis (CKD-ND), the QM use of DA for anaemia correction has not been previously investigated., Methods: In this randomized, double-blind, non-inferiority, active-controlled study, adult subjects with CKD-ND, Hb levels <10 g/dL, and not treated with an erythropoiesis-stimulating agent were randomized 1:1 to receive DA every 2 weeks (Q2W) or QM for 33 weeks with initial doses of 0.75 μg/kg Q2W or 1.5 μg/kg QM. Subjects were treated to target Hb levels of 10-12 g/dL and ≥1 g/dL increase from baseline. The primary end-point was Hb change between baseline and the evaluation period (weeks 29-33), with a non-inferiority margin of -0.5 g/dL., Results: Three hundred and fifty-five subjects received ≥1 dose of DA. Mean (95% confidence interval [CI]) change in Hb between baseline and the evaluation period was 2.16 (1.98-2.33) g/dL for the Q2W group and 1.97 (1.80-2.14) g/dL for the QM group, the mean (95% CI) difference in Hb change being -0.19 (-0.43 to 0.05) g/dL. Most subjects (97.9% Q2W; 98.1% QM) achieved a Hb level ≥10.0 g/dL and ≥1.0 g/dL increase in Hb from baseline. Mean DA (SD) weekly equivalent doses over the evaluation period were 0.20 (0.23) and 0.27 (0.31) μg/kg per week for the Q2W and QM groups, respectively. Safety profiles were similar between groups., Conclusion: In subjects with CKD-ND, QM dosing was non-inferior to Q2W dosing for anaemia correction and had a similar safety profile., (© 2014 Asian Pacific Society of Nephrology.)

Objectives: The CHOICE study was a prospective, multicentre, observational study designed to assess the level of adherence in current clinical practice to the European product label and the EORTC guidelines for the treatment of chemotherapy-induced anaemia with darbepoetin alfa (DA)., Methods: Hb levels and red blood cell (RBC) transfusion requirements were evaluated among 1900 patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10-≤12 g/dL after 9 weeks' DA treatment., Results: The full analysis set (FAS) comprised 1887 patients (mean ± SD age 62.4 ± 11.4 years) divided into categories by baseline Hb < 9 g/dL (n = 281); 9-<10 g/dL (n = 770); 10-<11 g/dL (n = 695); ≥11 g/dL (n = 114). The proportion of patients who remained on the study at week 9 achieving the target Hb level was 37% (n = 60), 48% (n = 217), 54% (n = 210) and 38% (n = 23) in the subgroups with a baseline Hb level of <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL, respectively. In the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL subgroups of the FAS, the number of patients maintaining Hb levels ≥10 g/dL after their first achievement of an Hb value of 10 g/dL was 95 (34%), 372 (48%), 476 (68%) and 87 (76%), respectively. The Kaplan-Meier percentages of patients who required an RBC transfusion from week 5 until end of treatment period were: 29%, 20%, 12% and 17% in the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL subgroups, respectively. Kaplan-Meier percentages of patients reaching an Hb level of >13 g/dL were 10%, 9%, 21% and 29%, respectively. Potential bias could not be excluded due to the study's observational nature., Conclusions: DA initiation and target Hb ranges adhered to current guidelines in the majority of patients. Furthermore, this study demonstrates faster achievement of the target range and reduced transfusion requirements are associated with initiation of DA at Hb levels of 9-<10 g/dL and 10-<11 g/dL rather than <9 g/dL.

Objectives: The CHOICE study was a prospective, multicentre, observational study designed to assess levels of adherence in current clinical practice to the European product label and EORTC guidelines for the treatment of chemotherapy-induced anaemia (CIA) with darbepoetin alfa (DA). Here we present data split by tumour types: breast, colorectal, ovarian and lung., Methods: Haemoglobin (Hb) levels and red blood cell transfusion requirements were evaluated among patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10-≤12 g/dL., Results: The full analysis set included 1887 patients (mean ± SD 62.4 ± 11.4 years); 1585 (84%) had a current disease stage of ≥3. Common chemotherapy regimens were non-platinum + non-taxane based (n = 696 [37%]) or platinum + non-taxane based (n = 660 [35%]). Breast cancer (n = 575): The mean ± SD Hb level at baseline was 9.9 ± 0.8 g/dL (n = 568). Target Hb level was reached by 187 (55%) patients. Colorectal cancer (n = 310): At baseline the mean ± SD Hb level was 9.8 ± 0.8 g/dL (n = 306). Target Hb level was reached by 107 patients (56%). Ovarian cancer (n = 301): The mean ± SD Hb level at baseline was 9.7 ± 0.8 g/dL (n = 294). Target Hb level was reached by 81 patients (44%). Lung cancer (n = 701): At baseline the mean ± SD Hb level was 9.8 ± 0.9 g/dL (n = 692). Target Hb level was reached by 142 patients (39%)., Safety: Five severe or life-threatening adverse drug reactions were seen (three patients with breast cancer, one patient with colorectal cancer and one patient with ovarian cancer)., Limitations: Potential bias could not be excluded due to the study's observational nature., Conclusions: This study demonstrates that the recommendations are adhered to in clinical practice, with the mean starting Hb level <10 g/dL irrespective of tumour type. Furthermore, DA is likely to be effective and well tolerated for the treatment of CIA in patients with breast, colorectal, ovarian or lung cancer.

Objective: To evaluate adherence to European Organisation for Research and Treatment of Cancer (EORTC) and European Summary of Product Characteristic (SmPC) guidance on recommended haemoglobin (Hb) values in routine clinical practice use of darbepoetin alfa (DA) in cancer patients internationally., Methods: This multicentre, prospective, observational study assessed DA use in 11 European countries. This interim analysis (IA) included ∼1300 breast, colorectal, ovarian or lung cancer patients receiving DA during any chemotherapy cycle. Hb level and red blood cell (RBC) transfusion requirement data were collected., Results: Of the 1290 patients (mean [SD] age 62.5 [11.1] years) included in this IA full analysis set, 499 had lung, 387 breast, 192 colorectal and 212 ovarian cancer. Mean baseline Hb levels were <10 g/dL. At week 9, 426 (33%) patients had a Hb level of 10-12 g/dL, 165 (13%) of >12 g/dL, 226 (18%) of <10 g/dL and 473 (37%) had missing Hb values. 54% of the 672 patients still on the study at week 9 with available Hb values had Hb values of 10-12 g/dL. For patients with a baseline Hb of <10 g/dL, the Kaplan-Meier (K-M) percentage of patients with Hb levels ≥10 g/dL from week 1 to end of treatment period (EOTP) was 86%. For these patients, the K-M% of patients with Hb levels >13 g/dL from week 1 to EOTP was 10%. The K-M% of patients requiring RBC transfusions from week 5 to EOTP was 26% for all patients. Seven patients reported treatment-related non-serious adverse drug reactions, four were thromboses., Conclusions: This IA suggests most patients were treated according to European SmPC guidance. Hb evolution during the study is consistent with data from clinical trials, implying DA is effective in increasing Hb levels in chemotherapy-induced anaemia patients. Hb levels >13 g/dL were infrequent. Limitations are related to the observational nature of this study.

Aims: Erythropoiesis-stimulating agents (ESAs) are recommended for managing renal anemia. ALTERNATE is an observational study in European and Australian dialysis patients evaluating darbepoetin a (DA) once every 2 weeks (Q2W) in clinical practice., Methods: Adult dialysis patients initiating treatment with DA Q2W were eligible regardless of previous/current ESA use. Data were collected 6 months before and 12 months after Q2W initiation. The primary endpoint was hemoglobin (Hb) concentration 12 months after initiation., Results: A total of 6,112 patients were enrolled; 6,104 were eligible (87% hemodialysis, 12% peritoneal dialysis). Before initiation, 77.3%, 8.8%, and 7.8% of patients were receiving DA, epoetin beta, and epoetin alpha, respectively; 6% were ESA naïve. Mean (95% CI) Hb (g/dl) was 11.68 (11.63-11.72) 6 months before initiation, 12.00 (11.97-12.04) at initiation, and 11.62 (11.58-11.66) 12 months after initiation. Geometric mean (95% CI) weekly ESA dose (µg/wk) was 27.27 (26.62-27.93) immediately before initiation, 23.69 (23.28 - 24.10) at initiation, and 26.80 (26.12-27.49) 12 months after initiation. At month 12, 77.3% of patients were receiving DA Q2W., Conclusions: This large observational study demonstrates that Hb concentrations can be effectively maintained over 12 months in a general dialysis population with DA Q2W without an increase in ESA dose.

Aim: Darbepoetin alfa has a longer half-life than epoetin-(EPO) alfa or beta, allowing administration at less frequent intervals for the treatment of renal anemia. The aim of the present analysis was to evaluate the efficacy and tolerability of an every-2-week (Q2W) schedule of darbepoetin alfa in a large cohort of dialysis patients., Methods: Data were combined from eight similarly designed 24-week phase 3b European studies, in which patients receiving EPO alfa or beta once-weekly were converted to Q2W darbepoetin alfa. Darbepoetin alfa dosage was titrated to maintain hemoglobin (Hb) between 10 and 13 g/dl and efficacy was evaluated during a 4-week evaluation period., Results: In the 1,101 patients assigned to Q2W darbepoetin alfa (i.v., n = 196, s.c., n = 905), mean (SD) Hb levels were 11.53 (0.77) g/dl at baseline and 11.35 (1.04) g/dl at evaluation (mean change in Hb -0.27 g/dl, 95% confidence interval 0.34, -0.20). Hb levels were maintained between 10 and 13 g/dl during evaluation in 85% of patients. Darbepoetin alfa doses were similar at baseline and evaluation, and the i.v. and s.c. routes were associated with similar efficacy and dose requirements. Darbepoetin alfa was well-tolerated., Conclusions: Q2W darbepoetin alfa is effective in maintaining Hb levels in dialysis patients switched from weekly rHuEPO, regardless of the route of administration and with no notable increase in the weekly equivalent dose.

Background: Equivalence of intravenous (i.v.) and subcutaneous (s.c.) dosage requirements is a notable characteristic of darbepoetin-alpha (DPO), as opposed to other epoetins (EPOs). Currently in Europe, the EPOs/DPO conversion factor (200 IU EPOs = 1 microg DPO) does not take into account the route of drugs administration. To better define this ratio we have conducted a prospective, long-term trial in a group of hemodialysis patients., Subjects and Methods: At the start, we evaluated 40 iron-replete hemodialysis patients, but the final study was performed in the remaining 25 patients. During the first 6 months, patients were on i.v. epoetin-alpha (EPOalpha) maintenance therapy (phase 1: T-6 to T0). After conversion to i.v. DPO (initial 200:1 ratio) the observation was prolonged for a period of 12 months (phase 2: T0 to T12). DPO was administered at extended dose intervals and the EPOalpha/DPO rate was adjusted every month to maintain hemoglobin (Hgb) stability. Iron status and factors inhibiting erythropoiesis were continually checked to exclude unstable patients., Results: Phase 1: EPOalpha weekly mean dose showed no significant variation. Phase 2: EPOalpha/DPO conversion factor progressively rose from 200 to 256.7 +/- 86.9 IU/microg at T7 (p<0.005) and 336.8 +/- 104.3 IU/microg at T12 (p<0.0005). DPO weekly mean dosage decreased from 40.0 +/- 12.0 microg/week at T0 to 31.6 +/- 3.7 microg/week at T7 (p<0.005) and 24.6 +/- 7.0 microg/week at T12 (p<0.0005). Mean weekly/patient acquisition cost of EPOalpha was euro 70.6 +/- 21.3 (T-6 to T0); after switching, the cost of DPO was euro 72.4 +/- 22.7 (T0) and fell to euro 53.1 +/- 11.2 during T6 to T12., Conclusions: The progressive increase of EPOalpha/DPO ratio demonstrated that i.v. DPO requires lower doses compared with i.v. EPOalpha. When drugs are administered i.v., the starting EPOalpha/DPO conversion factor should be increased over the 200:1 ratio, similar to recommendations outlined in the United States and Japan. DPO dose reduction translated to notable cost-savings.

The use of erythropoietic growth factors to treat chemotherapy-induced anemia (CIA) has been increasing as clinicians become more aware of the ability of these drugs to improve the quality of life of patients with cancer. The cost associated with erythropoietic growth factor therapy makes its appropriate use a practical issue for physicians and hospitals. Clinical practice guidelines can benefit physicians by increasing practice efficiency, reducing medical errors, increasing the quality of medical care, and decreasing reimbursement problems. The American Society of Clinical Oncology and the American Society of Hematology, the European Organisation for Research and Treatment of Cancer, and the National Comprehensive Cancer Network (NCCN) have all published guidelines for using erythropoietic growth factors to treat CIA, and this article reviews and summarizes those guidelines. Of the three guidelines for the use of erythropoietic growth factors in CIA, the NCCN guidelines are based on the most recent data. Current evidence indicates that erythropoietic growth factors can increase hemoglobin levels, reduce the need for red blood cell transfusions, and improve quality of life; the effect of erythropoietic therapy on outcomes in patients with CIA is still being investigated.

Background: In the United States, darbepoetin alfa (Aranesp) is often used to treat patients with chemotherapy-induced anemia using weekly or every-2-week administration schedules. In Europe, darbepoetin alfa is used either weekly or in every-3-week dosing. The every-3-week schedule can be synchronized with many chemotherapy regimens, resulting in fewer visits and reducing burden to patients, but the safety and efficacy of this regimen have not been clear., Methods: A randomized, double-blind, double-dummy, active-controlled phase 3 trial was performed in 110 European centers. Eligible patients (age > or = 18 years) were anemic (hemoglobin level < 11 g/dL), had a nonmyeloid malignancy, and were to receive at least 12 weeks of chemotherapy. Patients were randomly assigned 1:1 to darbepoetin alfa treatment every 3 weeks (500-microg dose) or weekly (2.25-microg/kg) for 15 weeks. We compared red blood cell transfusion incidence among the two arms from week 5 to the end of the treatment phase using a noninferiority study design. Noninferiority was determined if the upper limit of the 95% confidence interval (CI) for the difference in blood transfusions between groups, calculated using Kaplan-Meier methods, did not exceed 12.5%, a margin based on previous placebo-controlled studies., Results: A total of 705 patients were randomly assigned, and 672 remained in the study at week 5. Fewer patients in the every-3-week arm than in the weekly arm received blood transfusions from week 5 to the end of the treatment phase (unadjusted Kaplan-Meier estimates = 23% versus 30%, difference = -6.8%; 95% CI = -13.6 to 0.1). Percentages of patients achieving the target hemoglobin level (> or = 11 g/dL, consistent with evidence-based practice guidelines) were 84% (every 3 weeks) and 77% (weekly). The frequency of cardiovascular/thromboembolic adverse events was 8% in both groups, and safety was comparable., Conclusions: Patients with chemotherapy-induced anemia can safely and effectively be treated with 500 microg of darbepoetin alfa every 3 weeks.