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Iain C. Macdougall - One of the best experts on this subject based on the ideXlab platform.
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maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol epoetin beta versus Darbepoetin Alfa administered monthly a randomized comparative trial
Nephrology Dialysis Transplantation, 2010Co-Authors: Fernando Carrera, Iain C. Macdougall, Peter G. Kerr, Johannes F.e. Mann, Giuseppe Villa, Francesco Locatelli, Bernard Canaud, Angel L M De Francisco, Anatole Besarab, Isabelle KazesAbstract:BACKGROUND: Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and Darbepoetin Alfa administered once monthly. METHODS: Haemodialysis patients (n = 490) on stable once-weekly intravenous Darbepoetin Alfa were randomized to methoxy polyethylene glycol-epoetin beta once monthly or Darbepoetin Alfa every 2 weeks for 26 weeks, with dose adjustment for individual haemoglobin target (11-13 g/dL; maximum decrease from baseline 1 g/dL). Subsequently, patients entered a second 26-week period of once-monthly methoxy polyethylene glycol-epoetin beta and Darbepoetin Alfa. The primary endpoint was the proportion of patients who maintained average haemoglobin ≥10.5 g/dL, with a decrease from baseline ≤1 g/dL, in Weeks 50-53; the secondary endpoint was dose change over time. The trial is registered at www.ClinicalTrials.gov, number NCT00394953. RESULTS: Baseline characteristics were similar between groups. One hundred and fifty-seven of 245 patients treated with methoxy polyethylene glycol-epoetin beta and 99 of 245 patients with Darbepoetin Alfa met the response definition (64.1% and 40.4%; P < 0.0001). Doses increased by 6.8% with methoxy polyethylene glycol-epoetin beta and 58.8% with Darbepoetin Alfa during once-monthly treatment. Death rates were equal between treatments (5.7%). Most common adverse events included hypertension, procedural hypotension, nasopharyngitis and muscle spasms, with no differences between groups. CONCLUSIONS: Methoxy polyethylene glycol-epoetin beta maintained target haemoglobin more successfully than Darbepoetin Alfa at once-monthly dosing intervals despite dose increases with Darbepoetin Alfa
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pharmacology of Darbepoetin Alfa
Nephrology Dialysis Transplantation, 2007Co-Authors: Iain C. Macdougall, Desmond Padhi, Graham JangAbstract:The distinct molecular structure of Darbepoetin Alfa, in both its amino acid sequence and its carbohydrate content, results in a biologic profile with lower binding affinity, longer circulating half-life, and higher in vivo potency compared with the epoetins. The mechanisms responsible for these differences in biological effects have not been fully explained. Pharmacokinetic investigations of Darbepoetin Alfa using prolonged blood sampling times established that the mean terminal half-life after subcutaneous (SC) administration is 70 to 105 hours. Pharmacodynamic studies were conducted to assess the suitability of Darbepoetin Alfa for use in weekly or less frequent (once every other week or once a month) dosing regimens to maintain haemoglobin levels in patients with anaemia of renal disease. Regardless of dialysis status, route of administration, or prior treatment with an erythropoiesis-stimulating agent, Darbepoetin Alfa administered at extended intervals was able to raise or maintain hemoglobin levels to target. More rigorous studies will be needed to confirm these findings.
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correction of anaemia with Darbepoetin Alfa in patients with chronic kidney disease receiving dialysis
Nephrology Dialysis Transplantation, 2003Co-Authors: Iain C. Macdougall, James Matcham, Stephen J GrayAbstract:BACKGROUND: Darbepoetin Alfa is a new recombinant erythropoietic protein with a 3-fold longer half-life than recombinant human erythropoietin (rHuEpo). The optimal starting dose and frequency of administration of Darbepoetin Alfa were investigated for treating renal anaemia in dialysis patients. METHODS: Two multicentre, sequential dose-escalation studies examined the i.v. route of administration of Darbepoetin Alfa in haemodialysis patients (n=75) and the s.c. route in peritoneal dialysis patients (n=47). Patients were randomized to receive Darbepoetin Alfa at doses ranging from 0.075 to 0.75 microg/kg/week administered as either a once weekly or a three-times weekly injection. Patients achieving the primary endpoint of a > or = 1 g/dl increase in haemoglobin after 4 weeks continued Darbepoetin Alfa for up to 52 weeks. Safety was assessed by adverse event reports, changes in laboratory values and vital signs, and antibody screening. RESULTS: Darbepoetin Alfa produced dose-related increases in haemoglobin over the first 4 weeks of treatment in both studies. Two dose levels (0.45 and 0.75 microg/kg/week) increased the haemoglobin by > or = 1 g/dl in 60-80% of patients, and no difference between once weekly and three-times weekly dosing was apparent. For patients who continued treatment up to 52 weeks, haemoglobin was maintained between 10 and 13 g/dl from mean baseline values of 8.4 and 8.7 g/dl. The adverse event profile was similar to that associated with rHuEpo therapy, and no antibodies to Darbepoetin Alfa were detected. CONCLUSIONS: Darbepoetin Alfa is safe and effective for the treatment of anaemia in dialysis patients. The optimal weekly starting dose is 0.45-0.75 microg/kg and once weekly dosing is possible for both the s.c. and i.v. routes of administration.
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Darbepoetin Alfa: a new therapeutic agent for renal anemia.
Kidney International, 2002Co-Authors: Iain C. MacdougallAbstract:Darbepoetin Alfa: A new therapeutic agent for renal anemia. Darbepoetin Alfa is a super-sialylated analog of human erythropoietin that has a longer circulating half-life in vivo compared to both native and recombinant hormone. It has the same mechanism of action as erythropoietin, stimulating the same surface membrane receptor and triggering the same intracellular chain of events. An extra two N-linked carbohydrate chains, however, gives Darbepoetin Alfa greater metabolic stability in vivo, and its terminal half-life after intravenous administration is approximately three times longer than for intravenous erythropoietin. This in turn allows injections of the drug to be given less frequently, and studies have shown that once-weekly and once-every-other-week dosing can maintain the hemoglobin concentration in patients with renal anemia. The recommended starting dose for Darbepoetin Alfa is 0.45 μg/kg once weekly for both IV and SC administration, with subsequent titration based on the hemoglobin concentration. The adverse event profile is very similar to that seen with rHuEPO, and no antibodies have been detected in several thousand patients exposed to the drug, some of whom have been treated for up to five years now. Following a clinical research program that began in November 1996, Darbepoetin Alfa was finally approved by the European Commission in June 201, and by the FDA in September 201.
G. Rossi - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics of Darbepoetin Alfa after intravenous or subcutaneous administration in patients with non-myeloid malignancies undergoing chemotherapy.
Clinical Pharmacokinectics, 2013Co-Authors: Anne C Heatherington, G. Rossi, John T. Sullivan, Christian Dittrich, Johannes SchuellerAbstract:Background and objective The pharmacokinetics of Darbepoetin Alfa after intravenous (IV) administration in the oncology setting have not been previously reported. The objective of this study was to evaluate the pharmacokinetics of IV or subcutaneous (SC) Darbepoetin Alfa in patients with non-myeloid malignancies undergoing multicycle chemotherapy.
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Pharmacokinetic evaluation of Darbepoetin Alfa for the treatment of pediatric patients with chemotherapy‐induced anemia
Pediatric Blood & Cancer, 2007Co-Authors: Jeffrey L Blumer, Thomas Loew, Stacey L. Berg, Peter C Adamson, G. Rossi, Caroline A. HastingsAbstract:Background Cancer patients undergoing chemotherapy often develop anemia, which can increase the risk for transfusions and fatigue. The recombinant erythropoiesis-stimulating agent Darbepoetin Alfa can effectively treat chemotherapy-induced anemia (CIA) in adults, but limited data are available regarding its use in pediatric cancer patients. The goals of this phase 1, open-label, uncontrolled study were to assess the pharmacokinetic profile and safety of Darbepoetin Alfa in pediatric patients with CIA. Procedure Pediatric patients with nonmyeloid malignancies and CIA received up to six doses of Darbepoetin Alfa 2.25 mcg/kg subcutaneously. After the first dose, the pharmacokinetic properties of Darbepoetin Alfa were assessed during a 14-day sampling period. All subsequent doses were given weekly with predose blood samples collected before study drug administration. Results After a single dose of Darbepoetin Alfa, the mean (SD) peak serum concentration was 10.5 (3) ng/ml, and the median time to peak concentration was 71.4 hr. Darbepoetin Alfa exhibited a mean (SD) terminal half-life of 49.4 (32) hr. Upon repeated weekly administration, no evidence of Darbepoetin Alfa accumulation was observed though there was high intra- and inter-individual variability. In addition, Darbepoetin Alfa was well tolerated; some study patients experienced increases in hemoglobin. Conclusions The pharmacokinetic profile of Darbepoetin Alfa indicated that it was slowly absorbed and exhibited a long terminal half-life in these pediatric study patients with CIA. Pediatr Blood Cancer 2007;49:687–693. © 2006 Wiley-Liss, Inc.
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Pharmacokinetic evaluation of Darbepoetin Alfa for the treatment of pediatric patients with chemotherapy-induced anemia.
Pediatric Blood & Cancer, 2007Co-Authors: Jeffrey L Blumer, Thomas Loew, Stacey L. Berg, Peter C Adamson, G. Rossi, Caroline A. HastingsAbstract:Background Cancer patients undergoing chemotherapy often develop anemia, which can increase the risk for transfusions and fatigue. The recombinant erythropoiesis-stimulating agent Darbepoetin Alfa can effectively treat chemotherapy-induced anemia (CIA) in adults, but limited data are available regarding its use in pediatric cancer patients. The goals of this phase 1, open-label, uncontrolled study were to assess the pharmacokinetic profile and safety of Darbepoetin Alfa in pediatric patients with CIA. Procedure Pediatric patients with nonmyeloid malignancies and CIA received up to six doses of Darbepoetin Alfa 2.25 mcg/kg subcutaneously. After the first dose, the pharmacokinetic properties of Darbepoetin Alfa were assessed during a 14-day sampling period. All subsequent doses were given weekly with predose blood samples collected before study drug administration. Results After a single dose of Darbepoetin Alfa, the mean (SD) peak serum concentration was 10.5 (3) ng/ml, and the median time to peak concentration was 71.4 hr. Darbepoetin Alfa exhibited a mean (SD) terminal half-life of 49.4 (32) hr. Upon repeated weekly administration, no evidence of Darbepoetin Alfa accumulation was observed though there was high intra- and inter-individual variability. In addition, Darbepoetin Alfa was well tolerated; some study patients experienced increases in hemoglobin. Conclusions The pharmacokinetic profile of Darbepoetin Alfa indicated that it was slowly absorbed and exhibited a long terminal half-life in these pediatric study patients with CIA. Pediatr Blood Cancer 2007;49:687–693. © 2006 Wiley-Liss, Inc.
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efficacy and safety of every 2 week Darbepoetin Alfa in patients with anemia of cancer a controlled randomized open label phase ii trial
Oncologist, 2007Co-Authors: Veena Charu, Dianne Tomita, G. Rossi, Chandra P Belani, Ahmad N Gill, Mukesh Bhatt, Ali BenjacobAbstract:This randomized, controlled trial evaluated the effect of DarbepoetinAlfaonhospitalizationdays,transfusionrequirements, hemoglobin levels, and fatigue in patients with anemia of cancer (AOC). Eligible patients were anemic (hemoglobin 18 years old, and had not received chemotherapy or radiotherapy within 4 weeks of study screening. Patients were randomized 4:1 to receive Darbepoetin Alfa, 3.0 g/kg every 2 weeks (Q2W) (n 226), or observation only for 12 weeks (n 59), followed by an optional 9 weeks of Darbepoetin Alfa, 3.0 g/kg Q2W. Endpoints were compared between the two treatment arms at week 13. A planned interim analysis indicated that assumptions regarding hospitalization in the study design were incorrect, so the study was terminated early. Therefore, results for the primary endpoint should be interpreted cautiously. The hospitalization rate was similar (0.5 days) for both the Darbepoetin Alfa and observation groups (p .73). Transfusion incidence (weeks 5–12) was significantly lower for Darbepoetin Alfa patients (8%) than for observation patients (22%) (p .0092). Byweek13,hemoglobinincreasedby2.1g/dlinpatients receiving Darbepoetin Alfa, compared with 0.1 g/dl in the observation group p < .0001. Hemoglobin improvements were paralleled by an increase in Functional Assessment of Cancer Therapy–Fatigue score (mean change in score at week 13: Darbepoetin Alfa, 6.0; observation, 2.2; p < .05). Darbepoetin Alfa Q2W can significantly improve hemoglobin levels and reduce transfusion requirements in patients with AOC, resulting in significant improvements in health-related quality of life. The Oncologist 2007;12:727–737
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A retrospective cohort study to assess the impact of therapeutic substitution of Darbepoetin Alfa for epoetin Alfa in anemic patients with myelodysplastic syndrome.
The journal of supportive oncology, 2005Co-Authors: Jeffrey F Patton, G. Rossi, Toni Sullivan, Timothy Reeves, Joel F. WallaceAbstract:: Darbepoetin Alfa and epoetin Alfa are used to treat anemia in the undertreated population of patients with myelodysplastic syndrome (MDS). We implemented guidelines to switch anemic patients with MDS from epoetin Alfa 40,000 U weekly to Darbepoetin Alfa 200 microg every 2 weeks and then conducted a retrospective cohort study of the initial 263 treated patients. Patients (> or = 18 years old, MDS diagnosis) were either previously treated with epoetin Alfa (received 16 weeks of prior epoetin Alfa and either switched to Darbepoetin Alfa or remained on epoetin Alfa) or treatment-naive (no previous erythropoietin therapy and received only 1 agent for 16 weeks). Both major response and minor response based on the International Working Group criteria were calculated. The study was not powered to statistically compare treatment groups; values presented are for descriptive purposes only. Data from 244 patient records were included: 142 previous epoetin Alfa patients (80 switched to Darbepoetin Alfa, 62 remained on epoetin Alfa) and 102 naive patients (56 Darbepoetin Alfa, 46 epoetin Alfa). Major response rates were similar between treatment groups in both the naive (46% for Darbepoetin Alfa, 35% for epoetin Alfa) and previous epoetin Alfa groups (26% for Darbepoetin Alfa, 17% for epoetin Alfa). Overall response rates were 42%-76% across treatment groups. No differences in transfusions across groups were observed. Treatment of anemic patients with MDS with either Darbepoetin Alfa or epoetin Alfa appeared to be effective. Whereas epoetin Alfa was most frequently administered on a weekly basis, Darbepoetin Alfa was most frequently administered every 2 weeks, which may offer the benefit of convenience with its less frequent dosing.
John A Glaspy - One of the best experts on this subject based on the ideXlab platform.
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Darbepoetin Alfa administered every 2 weeks alleviates anemia in cancer patients receiving chemotherapy.
Oncology (Williston Park N.Y.), 2020Co-Authors: John A Glaspy, N S TchekmedyianAbstract:The objectives of this study were to assess the safety and efficacy of Darbepoetin Alfa (Aranesp) administered every 2 weeks in anemic patients with solid tumors receiving chemotherapy. This was an open-label, randomized, active-controlled, multicenter dose-finding study evaluating a range of every-2-week Darbepoetin Alfa doses. The active control arm received epoetin Alfa (Epogen, Procrit) at 40,000 U weekly with a dose increase to 60,000 U weekly for subjects with an inadequate response. The lowest clinically effective doses of Darbepoetin Alfa in this study were 3.0 and 5.0 microg/kg every 2 weeks, with no additional benefit observed at higher doses. The percentage of patients who achieved a hematopoietic response in the 3.0- and 5.0-microg/kg groups was 66% (95% confidence interval [CI] = 46%-86%) and 84% (95% CI = 67%-100%), respectively, compared with 63% (95% CI = 46%-81%) in the epoetin Alfa group. Darbepoetin Alfa administered at a dose of 3.0 microg/kg every 2 weeks is safe and effective for treating anemia in patients with solid tumors on chemotherapy, and is comparable to epoetin Alfa. A dose increase to 5.0 microg/kg of Darbepoetin Alfa administered every 2 weeks may be appropriate in patients with an inadequate initial response.
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effects of chemotherapy on endogenous erythropoietin levels and the pharmacokinetics and erythropoietic response of Darbepoetin Alfa a randomised clinical trial of synchronous versus asynchronous dosing of Darbepoetin Alfa
European Journal of Cancer, 2005Co-Authors: John A Glaspy, David H Henry, Ravi Patel, Simon Tchekmedyian, Steve Applebaum, Donald Berdeaux, Richard Lloyd, Russell Berg, Matthew Austin, G. RossiAbstract:Abstract The introduction of longer-acting erythropoietic agents into the practice of oncology has demanded an understanding of the interaction of chemotherapy with the pharmacokinetics and haematological effects of these erythropoietins. We report results of a randomised trial comparing the haematological effects of Darbepoetin Alfa, 6.75 μg/kg, administered once every 3 weeks to anaemic cancer chemotherapy patients on either an asynchronous (day 15) or synchronous (day 1) schedule relative to their every-3-week chemotherapy. A total of 81 patients were randomised and received the study drug (43 asynchronous; 38 synchronous). No difference was observed between groups in the primary endpoint of mean haemoglobin change after 6 weeks of therapy (P = 0.45) and change scores were similar to those observed with standard weekly Darbepoetin Alfa therapy. In a subset of patients evaluated with intensive pharmacokinetic sampling, an increase in endogenous erythropoietin concentration (up to 4-fold) lasting approximately 1 week following chemotherapy administration was observed in both groups. Synchronous administration of Darbepoetin Alfa was associated with a 1.3-fold increase in the area under the Darbepoetin Alfa concentration–time curve compared with asynchronous administration. Our data suggest that Darbepoetin Alfa is effective administered every 3 weeks regardless of timing of administration with respect to chemotherapy and that receptor-mediated uptake by the erythron may be an important clearance mechanism for erythropoietic proteins.
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comparison of the isoelectric focusing patterns of Darbepoetin Alfa recombinant human erythropoietin and endogenous erythropoietin from human urine
Clinical Chemistry, 2002Co-Authors: Don H Catlin, Andreas Breidbach, Steve Elliott, John A GlaspyAbstract:Novel erythropoiesis-stimulating protein (AranespTM; Darbepoetin Alfa) is a glycoprotein hormone with a longer serum half-life than recombinant human erythropoietin (rHuEPO) (1). The polypeptide backbone of the human EPO molecule has an invariant amino acid sequence; however, the carbohydrate side chains exhibit microheterogeneity in sugar content and structure (2)(3)(4). A negatively charged sialic acid molecule typically caps the end of each arm of a carbohydrate chain. As a consequence, the variable nature of the sialic acid content gives rise to EPO isoforms with differences in charge (3). After purifying isoforms of rHuEPO, Egrie and coworkers (5)(6) discovered a direct correlation between the number of sialic acid groups on the carbohydrate part of rHuEPO and both its serum half-life and biological activity, as well as an inverse relationship with receptor binding. These data showed that pharmacokinetic factors have a greater influence on biological activity than receptor binding affinity. These principles explain the increased half-life and increased in vivo activity of Darbepoetin Alfa, which contains 5 N-linked carbohydrate chains and up to 22 sialic acids (5)(7). In contrast, rHuEPO has 3 N-linked carbohydrate chains and a maximum of 14 sialic acids (5)(7). Similar clinical responses can be achieved by administering Darbepoetin Alfa once a week or rHuEPO three times a week (8)(9). The efficacy of Darbepoetin Alfa in the treatment of anemia associated with chronic renal failure has been shown (10), and in 2001 it was approved by the US Food and Drug Administration for that indication. Darbepoetin Alfa is under investigation for the treatment of anemia in cancer patients (11) and other applications. Although Darbepoetin Alfa was approved only recently, we detected Darbepoetin Alfa in the urine of three athletes competing in the 2002 Winter Olympic Games …
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Darbepoetin Alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy
British Journal of Cancer, 2002Co-Authors: John A Glaspy, J Jadeja, Glen R Justice, J Kessler, D Richards, Lee S Schwartzberg, N S Tchekmedyian, S Armstrong, J Obyrne, G. RossiAbstract:In part A of this study, patients were randomised to cohorts receiving Darbepoetin Alfa at doses of 0.5 to 8.0 m.c.g x kg(-1) x wk(-1) or to a control group receiving epoetin Alfa at an initial dose of 150 U x kg(-1) three times weekly. In part B, the cohorts were Darbepoetin Alfa 3.0 to 9.0 m.c.g x kg(-1) every 2 weeks or epoetin Alfa, initial dose 40 000 U x wk(-1). Safety was assessed by adverse events, changes in blood pressure, and formation of antibodies to Darbepoetin Alfa. Efficacy was assessed by several haematologic endpoints, including change in haemoglobin from baseline. The adverse event profile of Darbepoetin Alfa was similar to that of epoetin Alfa. No relationship between the rapidity of haemoglobin response and any adverse event was observed. No antibodies to Darbepoetin Alfa were detected. Higher doses of Darbepoetin Alfa increased the proportion of patients with a haemoglobin response and decreased the median time to response. The overall dose of Darbepoetin Alfa required to produce a mean increase in haemoglobin does not increase when the dosing interval is increased from 1 to 2 weeks. Therapy with Darbepoetin Alfa is safe and effective in producing a dose-related increase in haemoglobin levels in patients with cancer receiving chemotherapy.
Dianne Tomita - One of the best experts on this subject based on the ideXlab platform.
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randomized double blind placebo controlled trial of every 3 week Darbepoetin Alfa 300 micrograms for treatment of chemotherapy induced anemia
Current Medical Research and Opinion, 2009Co-Authors: Enrique Hernandez, Veena Charu, Tom Lillie, Dianne Tomita, Joseph Dibenedetto, Peter Ganly, Kerry TaylorAbstract:ABSTRACTObjective: Darbepoetin Alfa is effective in treating chemotherapy-induced anemia (CIA). Administration of subcutaneous Darbepoetin Alfa every 3 weeks (Q3W) could simplify treatment through synchronization with common Q3W chemotherapy regimens. We report results from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of fixed-dose Q3W Darbepoetin Alfa in patients with a wide variety of tumor types who experienced CIA.Research design and methods: Patients aged ≥ 18 years with anemia (hemoglobin <11 g/dL) being treated for nonmyeloid malignancy were randomized 1:1 to receive Darbepoetin Alfa 300 μg (n = 193) or placebo (n = 193) subcutaneously Q3W from weeks 1 to 13 in this 16-week study. Doses could be adjusted per prespecified rules.Main outcome measures: The primary endpoint was the proportion of patients who received ≥1 red blood cell (RBC) transfusion between week 5 and the end of the treatment period (EOTP). The study also analyzed the ...
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efficacy and safety of every 2 week Darbepoetin Alfa in patients with anemia of cancer a controlled randomized open label phase ii trial
Oncologist, 2007Co-Authors: Veena Charu, Dianne Tomita, G. Rossi, Chandra P Belani, Ahmad N Gill, Mukesh Bhatt, Ali BenjacobAbstract:This randomized, controlled trial evaluated the effect of DarbepoetinAlfaonhospitalizationdays,transfusionrequirements, hemoglobin levels, and fatigue in patients with anemia of cancer (AOC). Eligible patients were anemic (hemoglobin 18 years old, and had not received chemotherapy or radiotherapy within 4 weeks of study screening. Patients were randomized 4:1 to receive Darbepoetin Alfa, 3.0 g/kg every 2 weeks (Q2W) (n 226), or observation only for 12 weeks (n 59), followed by an optional 9 weeks of Darbepoetin Alfa, 3.0 g/kg Q2W. Endpoints were compared between the two treatment arms at week 13. A planned interim analysis indicated that assumptions regarding hospitalization in the study design were incorrect, so the study was terminated early. Therefore, results for the primary endpoint should be interpreted cautiously. The hospitalization rate was similar (0.5 days) for both the Darbepoetin Alfa and observation groups (p .73). Transfusion incidence (weeks 5–12) was significantly lower for Darbepoetin Alfa patients (8%) than for observation patients (22%) (p .0092). Byweek13,hemoglobinincreasedby2.1g/dlinpatients receiving Darbepoetin Alfa, compared with 0.1 g/dl in the observation group p < .0001. Hemoglobin improvements were paralleled by an increase in Functional Assessment of Cancer Therapy–Fatigue score (mean change in score at week 13: Darbepoetin Alfa, 6.0; observation, 2.2; p < .05). Darbepoetin Alfa Q2W can significantly improve hemoglobin levels and reduce transfusion requirements in patients with AOC, resulting in significant improvements in health-related quality of life. The Oncologist 2007;12:727–737
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Darbepoetin Alfa Administered Every Three Weeks Is Effective for the Treatment of Chemotherapy-Induced Anemia
Oncologist, 2006Co-Authors: Ralph V Boccia, Tom Lillie, Dianne Tomita, Imtiaz A. Malik, Vinay Raja, Stephen Kahanic, Billy Clowney, Peter T. SilbersteinAbstract: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 μg) Q3W in patients with CIA. Eligible patients (≥18 years) were anemic (hemoglobin
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Darbepoetin Alfa administered every three weeks is effective for the treatment of chemotherapy induced anemia
Oncologist, 2006Co-Authors: Ralph V Boccia, Tom Lillie, Dianne Tomita, Imtiaz A. Malik, Vinay Raja, Stephen Kahanic, Billy Clowney, Peter T. SilbersteinAbstract: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 μg) Q3W in patients with CIA. Eligible patients (≥18 years) were anemic (hemoglobin <11 g/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 ≥10 g/dl) on clinical outcomes was evaluated. Patients in the ≥10-g/dl stratum achieved the hemoglobin target range (11–13 g/dl) in less time than patients in the <10-g/dl stratum (3 weeks vs. 9 weeks). More patients in the ≥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 ≥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 (≥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. The Oncologist 2006;11:409–417
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utilization of Darbepoetin Alfa and epoetin Alfa for chemotherapy induced anemia
American Journal of Health-system Pharmacy, 2005Co-Authors: James Douglas Herrington, Stephen L Davidson, Larry L Green, Dianne Tomita, Robert E Smith, Ralph V BocciaAbstract:Purpose. The patterns of use and effectiveness of therapy with Darbepoetin alpha and epoetin Alfa for chemotherapy-induced anemia (CIA) in hospital outpatient and community settings were evaluated. Methods. Data were collected from medical charts at 65 oncology clinics in hospital outpatient and comunity settings for consecutive patients who received the first dose of either Darbepoetin Alfa or epoetin Alfa between August 1, 2002, and February 15, 2003, and were to have 12 weeks of follow-up data. Results. Data from the charts of 3123 patients were abstracted. Of these patients, 2785 were treated with only one erythropoietic agent (1444 with Darbepoetin Alfa and 1341 with epoetin Alfa) and were included in the analysis. The most common initial dosage of Darbepoetin Alfa was 200 μg every two weeks (61% of Darbepoetin Alfa recipients), and the most common initial dasage of epoetin Alfa was 40, 000 units weekly (72%). With these regimens, the dosage was escalated for 22% of epoetin Alfa recipients at a median of six weeks after the initial dose. The mean change from baseline in hemoglobin concentration after 12 weeks of therapy was similar for both groups, as was the percent of patients with red-blood-cell transfusions during treatment. Conclusion. The most common initial dosage of Darbepoetin Alfa for CIA was 200 μg every two weeks, and the most common initial dosage of epoetin Alfa was 40,000 units weekly. At these dosages, the two agents appear to have similar clinical effectiveness. Index terms : Anemia, Antineaplastic agents ; Darbepoetin Alfa ; Dosage ; Drug comparisons ; Drug use ; Epoetin Alfa ; Hematopoietic agents ; Toxicity. Am J Health-Syst Pharm. 2005 ; 62:54-62
Stephen J Gray - One of the best experts on this subject based on the ideXlab platform.
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Darbepoetin Alfa administered once monthly maintains haemoglobin levels in stable dialysis patients
Nephrology Dialysis Transplantation, 2004Co-Authors: Michel Jadoul, Yves Vanrenterghem, Michel Foret, Rowan G Walker, Stephen J GrayAbstract:BACKGROUND: Darbepoetin Alfa, a glycoprotein that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin, has a 3-fold longer terminal half-life than recombinant human erythropoietin, allowing for an extended dosing interval. Darbepoetin Alfa is currently recommended for once-weekly and once every 2 weeks administration in patients with chronic renal failure (CRF). The objective of this study was to explore once-monthly administration in this patient population. METHODS: Clinically stable dialysis patients (mean haemoglobin concentration, 10.0-13.0 g/dl) receiving stable Darbepoetin Alfa therapy administered once every 2 weeks in a long-term treatment study were converted to Darbepoetin Alfa once every 3 weeks for 20 weeks and then, if haemoglobin concentrations were successfully maintained between 10.0 and 13.0 g/dl, were converted to Darbepoetin Alfa once every 4 weeks for 20 weeks. The Darbepoetin Alfa dose was titrated to maintain haemoglobin within a target range (-1.0 to +1.5 g/dl of baseline haemoglobin, and between 10.0 and 13.0 g/dl). Success with the extended dosing interval was defined as maintenance of mean haemoglobin >/=10.0 g/dl during a 4-week evaluation at the end of the dosing period. RESULTS: Of the 54 patients who entered the study, 38 patients were converted to Darbepoetin Alfa administered once every 4 weeks. Of these, 36 patients were considered evaluable and 30 (83%) of those evaluable patients successfully maintained the target haemoglobin. For successful patients the mean (SD) haemoglobin during evaluation was 11.16 (0.60) g/dl, and the mean change in haemoglobin from baseline to evaluation was -0.26 g/dl (95% CI: -0.51, -0.01). The median change from baseline in average weekly Darbepoetin Alfa dose was 1.61 microg (95% CI: 0.00, 4.75). Adverse events were consistent with those expected for this patient population. CONCLUSIONS: Darbepoetin Alfa, administered once monthly, maintained haemoglobin effectively and safely in most dialysis patients stabilized previously on once every 2 weeks dosing. Once-monthly dosing may optimize anaemia management for patients with CRF and for health care providers.
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correction of anaemia with Darbepoetin Alfa in patients with chronic kidney disease receiving dialysis
Nephrology Dialysis Transplantation, 2003Co-Authors: Iain C. Macdougall, James Matcham, Stephen J GrayAbstract:BACKGROUND: Darbepoetin Alfa is a new recombinant erythropoietic protein with a 3-fold longer half-life than recombinant human erythropoietin (rHuEpo). The optimal starting dose and frequency of administration of Darbepoetin Alfa were investigated for treating renal anaemia in dialysis patients. METHODS: Two multicentre, sequential dose-escalation studies examined the i.v. route of administration of Darbepoetin Alfa in haemodialysis patients (n=75) and the s.c. route in peritoneal dialysis patients (n=47). Patients were randomized to receive Darbepoetin Alfa at doses ranging from 0.075 to 0.75 microg/kg/week administered as either a once weekly or a three-times weekly injection. Patients achieving the primary endpoint of a > or = 1 g/dl increase in haemoglobin after 4 weeks continued Darbepoetin Alfa for up to 52 weeks. Safety was assessed by adverse event reports, changes in laboratory values and vital signs, and antibody screening. RESULTS: Darbepoetin Alfa produced dose-related increases in haemoglobin over the first 4 weeks of treatment in both studies. Two dose levels (0.45 and 0.75 microg/kg/week) increased the haemoglobin by > or = 1 g/dl in 60-80% of patients, and no difference between once weekly and three-times weekly dosing was apparent. For patients who continued treatment up to 52 weeks, haemoglobin was maintained between 10 and 13 g/dl from mean baseline values of 8.4 and 8.7 g/dl. The adverse event profile was similar to that associated with rHuEpo therapy, and no antibodies to Darbepoetin Alfa were detected. CONCLUSIONS: Darbepoetin Alfa is safe and effective for the treatment of anaemia in dialysis patients. The optimal weekly starting dose is 0.45-0.75 microg/kg and once weekly dosing is possible for both the s.c. and i.v. routes of administration.
