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Rossen Koytchev - One of the best experts on this subject based on the ideXlab platform.

  • switching Epoetin Alfa and Epoetin zeta in patients with renal anemia on dialysis posthoc analysis
    Advances in Therapy, 2010
    Co-Authors: Andrzej Wiecek, Islah Ahmed, Paul Scigalla, Rossen Koytchev
    Abstract:

    Introduction Epoetin zeta is a recently introduced recombinant erythropoietin, designed to be biologically similar to Epoetin Alfa. This posthoc analysis evaluated the impact of switching patients with chronic kidney disease (CKD) on hemodialysis from Epoetin Alfa to Epoetin zeta, or vice versa, on hemoglobin concentration, Epoetin dose, and patient safety.

  • comparison of the therapeutic effects of Epoetin zeta and Epoetin Alfa in the correction of renal anaemia
    Current Medical Research and Opinion, 2008
    Co-Authors: Stefan Krivoshiev, Paul Scigalla, Vasil V Todorov, Jacek Manitius, Stanislaw Czekalski, Rossen Koytchev
    Abstract:

    ABSTRACTObjective: To assess the therapeutic equivalence of Epoetin zeta and Epoetin Alfa for correction of haemoglobin (Hb) concentration in patients with anaemia and chronic kidney disease (CKD) stage 5 maintained on haemodialysis.Study design: In total, 609 patients with CKD and anaemia (Hb < 9 g/dL) were randomly assigned to receive either Epoetin zeta or Epoetin Alfa intravenously, one to three times per week for 24 weeks. Dosing was titrated individually to achieve a stable, target Hb concentration of 11–12 g/dL. Primary endpoints were the mean weekly dose of Epoetin per kilogram of body weight and mean Hb concentration during the last 4 weeks of treatment. Safety endpoints were the occurrence of anti-erythropoietin antibodies, ratings of tolerability and adverse events (AEs).Results: Mean (± standard deviation [SD]) Hb concentration over the last 4 weeks of treatment was 11.61 ± 1.27 g/dL for patients receiving Epoetin zeta, compared with 11.63 ± 1.37 g/dL for patients receiving Epoetin Alfa (95% c...

  • Comparison of the therapeutic effects of Epoetin zeta and Epoetin Alfa in the correction of renal anaemia
    Current Medical Research and Opinion, 2008
    Co-Authors: Stefan Krivoshiev, Paul Scigalla, Vasil V Todorov, Jacek Manitius, Stanislaw Czekalski, Rossen Koytchev
    Abstract:

    ABSTRACTObjective: To assess the therapeutic equivalence of Epoetin zeta and Epoetin Alfa for correction of haemoglobin (Hb) concentration in patients with anaemia and chronic kidney disease (CKD) stage 5 maintained on haemodialysis.Study design: In total, 609 patients with CKD and anaemia (Hb 

  • comparison of the therapeutic effects of Epoetin zeta to Epoetin Alfa in the maintenance phase of renal anaemia treatment
    Current Medical Research and Opinion, 2008
    Co-Authors: Volker Wizemann, Paul Scigalla, Boleslaw Rutkowski, C A Baldamus, Rossen Koytchev
    Abstract:

    OBJECTIVE: To evaluate the therapeutic efficacy and safety of Epoetin zeta, compared with Epoetin Alfa, in maintaining target haemoglobin (Hb) concentrations in patients with anaemia and chronic kidney disease (CKD) maintained on haemodialysis. METHODS: Patients received Epoetin zeta or Epoetin Alfa intravenously, 1-3 times/week for 12 weeks, then the alternative treatment for 12 weeks, in this double-blind, crossover, phase III trial. Eligible patients were 18-75 years old with CKD stage 5 maintained on haemodialysis. Patients had received Epoetin for > or = 3 months upon study entry and had achieved a target Hb level of 10.5-12.5 g/dL with a stable Epoetin dose. MAIN OUTCOME MEASURES: Primary efficacy endpoints were intra-individual differences (test-reference) in mean Hb levels and mean weekly dose/kg of body weight. Safety endpoints included occurrence of neutralizing anti-erythro poietin antibodies, tolerability, and adverse events (AEs). RESULTS: In total, 313 patients were randomized to receive Epoetin zeta (n = 155) or Epoetin Alfa (n = 158); 146 and 145 patients (respectively) switched treatment after 12 weeks. Mean (range) Hb levels were 11.35 (8.96-14.22) g/dL and 11.54 (8.74-13.84) g/dL for patients receiving Epoetin zeta and Epoetin Alfa, respectively (95% confidence interval [CI] [test-reference]: 0.09-0.28 g/dL, within the predefined equivalence range of +/-0.6 g/dL). Mean (range) weekly doses were 92.68 (12.74-398.41) IU/kg/wk and 92.58 (10.53-393.07) IU/kg/wk for patients receiving Epoetin zeta and Epoetin Alfa, respectively (95% CI [test-reference]: -4.67 and 4.29 IU/kg/wk, within the equivalence range of +/-45.00 IU/kg/wk). Patients underwent minor nominal dose adjustments during treatment crossover. AE profile was similar for both products; the most commonly reported AEs were infections and infestations (in 26.5% of patients receiving Epoetin zeta and 23.6% receiving Epoetin Alfa). No patients developed neutralizing anti-erythropoietin antibodies. CONCLUSIONS: Epoetin zeta is therapeutically equivalent to Epoetin Alfa in the maintenance of target Hb levels in patients with renal anaemia. No unexpected AEs were seen.

  • comparison of the therapeutic effects of Epoetin zeta to Epoetin Alfa in the maintenance phase of renal anaemia treatment
    Current Medical Research and Opinion, 2008
    Co-Authors: Volker Wizemann, Paul Scigalla, Boleslaw Rutkowski, C A Baldamus, Rossen Koytchev
    Abstract:

    ABSTRACTObjective: To evaluate the therapeutic efficacy and safety of Epoetin zeta, compared with Epoetin Alfa, in maintaining target haemoglobin (Hb) concentrations in patients with anaemia and chronic kidney disease (CKD) maintained on haemodialysis.Methods: Patients received Epoetin zeta or Epoetin Alfa intravenously, 1–3 times/week for 12 weeks, then the alternative treatment for 12 weeks, in this double-blind, crossover, phase III trial. Eligible patients were 18–75 years old with CKD stage 5 maintained on haemodialysis. Patients had received Epoetin for ≥ 3 months upon study entry and had achieved a target Hb level of 10.5–12.5 g/dL with a stable Epoetin dose.Main outcome measures: Primary efficacy endpoints were intra-individual differences (test–reference) in mean Hb levels and mean weekly dose/kg of body weight. Safety endpoints included occurrence of neutralizing anti-erythro­poietin antibodies, tolerability, and adverse events (AEs).Results: In total, 313 patients were randomized to receive epo...

John A Glaspy - One of the best experts on this subject based on the ideXlab platform.

  • benefits of Epoetin Alfa in anemic breast cancer patients receiving chemotherapy
    Clinical Breast Cancer, 2002
    Co-Authors: George D Demetri, Janice L Gabrilove, Michail V Blasi, Richard J Hill, John A Glaspy
    Abstract:

    Breast cancer patients receiving chemotherapy often exhibit anemia, which contributes to symptoms such as fatigue, compromising quality of life (QOL). The present subset analysis assessed the effects of recombinant human erythropoietin (rHuEPO, Epoetin Alfa) on anemia and QOL in approximately 1300 patients with breast cancer, who were derived from 3 large, community-based clinical trials of Epoetin Alfa in anemic chemotherapy patients with various malignancies. Epoetin Alfa effectively and safely corrected anemia and improved QOL scores on the Linear Analogue Self-Assessment, which measures energy, ability to perform daily activities, and QOL. Clinical, laboratory, and QOL improvements were qualitatively and quantitatively similar to those reported in the larger populations with various tumor types. The efficacy and safety of Epoetin Alfa did not vary according to dosing frequency (1 vs. 3 times weekly). Epoetin Alfa is, therefore, effective and safe in the management of anemia in patients with breast cancer treated with chemotherapy.

  • comparable efficacy of Epoetin Alfa for anemic cancer patients receiving platinum and nonplatinum based chemotherapy a retrospective subanalysis of two large community based trials
    Oncologist, 2002
    Co-Authors: John A Glaspy, Laurent Degos, Mario Dicato, George D Demetri
    Abstract:

    BACKGROUND Data from two large, community-based clinical trials that evaluated the efficacy of Epoetin Alfa in anemic cancer patients receiving chemotherapy were retrospectively analyzed to determine if clinical outcomes were different depending on whether chemotherapy was platinum- or nonplatinum-based. PATIENTS AND METHODS Patients received Epoetin Alfa 150-300 IU/kg (Glaspy: Study 1; n = 2,342) or 10,000-20,000 IU (Demetri: Study 2; n = 2,370) s.c. three times each week for 4 months. Efficacy end points were changes in transfusion requirements, hemoglobin (Hb) levels, and quality of life (QOL). A total of 4,298 out of 4,712 patients (platinum-based, n = 1,601; nonplatinum-based, n = 2,697), who both received chemotherapy and had available data, were eligible for this retrospective analysis. RESULTS Baseline characteristics across groups were comparable with few exceptions, which were anticipated in view of the characteristics of the two different chemotherapy types. Decreases in transfusion requirements after 2, 3, and 4 months were significant, regardless of chemotherapy type. Mean increases in Hb level from baseline to final evaluation ranged from 1.6 g/dl to 2.0 g/dl across study groups and were significant, regardless of chemotherapy type. QOL, as measured by the Linear Analog Scale Assessment (LASA), improved significantly by 20%-43%, regardless of chemotherapy type, and improvements were associated with increases in Hb. Epoetin Alfa was well tolerated in both studies, regardless of chemotherapy type. CONCLUSION Treatment of anemic cancer patients with Epoetin Alfa results in significant reduction in transfusion requirements, increase in Hb levels, and improvements in QOL, regardless of whether the chemotherapy is platinum- or nonplatinum-based.

  • clinical benefits of Epoetin Alfa therapy in patients with lung cancer
    Clinical Lung Cancer, 2002
    Co-Authors: Jeffrey Crawford, George D Demetri, Janice L Gabrilove, Michail V Blasi, Brenda Sarokhan, John A Glaspy
    Abstract:

    A retrospective subset analysis of anemic lung cancer patients who participated in three large, multicenter, community-based studies of 3-times-weekly (TIW) or once-weekly (QW) recombinant human erythropoietin (r-HuEPO, Epoetin Alfa) as an adjunct to chemotherapy was conducted. Patients were treated with Epoetin Alfa 150 U/kg in the first TIW study and with 10,000 U subcutaneously in the other study, with doubling of the dose if hemoglobin (Hb) response was inadequate. Patients in the QW study received Epoetin Alfa 40,000 U subcutaneously, which could be increased to 60,000 U. The maximum treatment duration for all three studies was 16 weeks. A total of 1748 lung cancer patients were evaluable for hematopoietic response; 1298 were evaluable for analyses of energy and 1300 were evaluable for analyses of activity and overall quality of life (QOL), as measured by the linear analogue scale assessment (LASA). Within 2 months of therapy, TIW and QW Epoetin Alfa therapy resulted in significant increases in Hb levels, decreases in transfusion requirements, and improvements in self-reported LASA scores. Increased Hb levels and reduced transfusion rates were demonstrated in the individual studies and in the analysis of data pooled from all three studies. Improvements in QOL parameters were significantly correlated with increased Hb levels. Epoetin Alfa was well tolerated in all studies. The clinical benefits and safety profiles of the TIW and the QW schedules appear to be similar. In addition, the QW schedule provides greater convenience to patients and physicians alike. Given the high incidence of anemia and transfusion utilization in patients presenting with lung cancer, Epoetin Alfa is an effective strategy for correcting anemia in these patients, thereby improving their energy levels, activity levels, and overall QOL.

  • the impact of Epoetin Alfa on quality of life during cancer chemotherapy a fresh look at an old problem
    Seminars in Hematology, 1997
    Co-Authors: John A Glaspy
    Abstract:

    Untreated anemia is common in cancer patients. Previous studies have demonstrated that both the existence of cancer and treatment with chemotherapy can suppress the normal endogenous erythropoietic response to anemia, making some cancer patients transfusion cadidates. In placebo-controlled phase III studies, administration of recombinant human erythropoietin (Epoetin Alfa) increased hemoglobin (Hb) levels and decreased transfusion requirements in patients undergoing cancer chemotherapy. In these studies, an increase in self-perceived energy level, functional status, and overall quality of life (QOL) was noted in the subset of patients in whom hematocrit levels increased by > or = 6%. To examine more closely the relationship between Epoetin Alfa therapy and QOL issues in patients undergoing chemotherapy, we conducted an open-label phase IV study involving 2,030 patients treated at 570 community cancer centers in the United States. Patients initially received Epoetin Alfa 150 U/kg subcutaneously (s.c.) three times per week for 4 months; if response was judged inadequate, the dosage was increased after 8 weeks to 300 U/kg s.c. three times per week. Hb levels and transfusion requirements were monitored monthly. Before and after the study, each patient completed a linear analog self-assessment scale designed to measure energy level, daily activity, and overall QOL. During Epoetin Alfa therapy, there was a progressive and significant increase (P < .001) in Hb concentrations. Significantly fewer (P < .001) patients were transfused and fewer transfusions were administered per patient per month after the first month of Epoetin Alfa therapy. Fifty-eight percent of the patients who required a transfusion during the first month of Epoetin Alfa therapy did not require a transfusion during the subsequent 3 months of the study. The entire patient population demonstrated a significant increase in mean scores for energy level, daily activity, and overall QOL. The magnitude of the increase in these scores correlated with the magnitude of the increase in Hb concentration. Statistically significant improvement in energy scores, daily activity, and overall QOL (P < .05) were observed, regardless of tumor response. These observations require confirmation on placebo-controlled trials, but the implications for oncology practice are important. They suggest that in cancer patients undergoing chemotherapy, the tradition of leaving anemia untreated may compromise patients' ability to function and their QOL.

  • impact of therapy with Epoetin Alfa on clinical outcomes in patients with nonmyeloid malignancies during cancer chemotherapy in community oncology practice procrit study group
    Journal of Clinical Oncology, 1997
    Co-Authors: John A Glaspy, Ronald M Bukowski, David Steinberg, Charles E Taylor, Simon Tchekmedyian, Saroj Vadhanraj
    Abstract:

    PURPOSETo study the impact of Procrit (Epoetin Alfa; Amgen Inc, Thousand Oaks, CA) on quality of life, transfusion requirements, and hemoglobin in anemic cancer patients receiving chemotherapy.PATIENTS AND METHODSMore than 500 community-based oncologists enrolled 2,342 patients with malignancies undergoing cytotoxic chemotherapy in an open-label study. Patients were treated with Epoetin Alfa 150 U/kg three times weekly, which could be doubled if the therapuetic response was judged inadequate. Total treatment was up to 4 months.RESULTSOf the 2,342 patients enrolled, data were available for 2,030 patients. Of the 2,030, 1,047 patients completed all 4 months of Epoetin Alfa therapy. Epoetin Alfa was associated with significant increases in mean self-rated scores for energy level, activity level, and overall quality of life; these improvements correlated with the magnitude of the hemoglobin increase and were independent of tumor response. In addition, Epoetin Alfa was associated with a significant increase in...

Robert Provenzano - One of the best experts on this subject based on the ideXlab platform.

  • roxadustat fg 4592 versus Epoetin Alfa for anemia in patients receiving maintenance hemodialysis a phase 2 randomized 6 to 19 week open label active comparator dose ranging safety and exploratory efficacy study
    American Journal of Kidney Diseases, 2016
    Co-Authors: Robert Provenzano, Anatole Besarab, Steven Wright, Steven Zeig, Peter Nguyen, Lona Poole, Khalil G Saikali, Gopal Saha, Stefan Hemmerich, Lynda A Szczech
    Abstract:

    Background Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. Study Design Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. Setting & Participants Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with Epoetin Alfa. Intervention Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous Epoetin Alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of Epoetin Alfa responsiveness. Intravenous iron was prohibited. Outcomes Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of −0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). Measurements Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). Results Baseline Epoetin Alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and Epoetin Alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the Epoetin Alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus Epoetin Alfa (P Limitations Short treatment duration and small sample size. Conclusions In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels.

  • extended Epoetin Alfa dosing as maintenance treatment for the anemia of chronic kidney disease the prompt study
    Clinical Nephrology, 2005
    Co-Authors: Robert Provenzano, Sarbani Bhaduri, Ajay K Singh
    Abstract:

    Aim To determine whether extended Epoetin Alfa dosing schedules of up to once every four weeks are as effective as weekly dosing in maintaining hemoglobin (Hb) levels in patients with anemia of chronic kidney disease (CKD). Methods This randomized, open-label trial enrolled patients with anemia of CKD not on dialysis. Patients were required to have a stable Hb level (> or = 11.0 g/dl) and to have been previously receiving Epoetin Alfa for two or more months. Patients were randomized to one of four subcutaneously administered Epoetin Alfa dosing regimens: 10,000 units (U) once weekly (QW), 20,000 U every two weeks (Q2W), 30,000 U every three weeks (Q3W) or 40,000 U every four weeks (Q4W). Dose reductions, but not escalations, were permitted. Patients received treatment for a total of 16 weeks. The primary endpoint for the trial was the mean final Hb measurements of the QW, Q2W, Q3W, and Q4W groups. The primary efficacy analyses were non-inferiority assessments of the mean final Hb measurements of the Q2W, Q3W, and Q4W groups, compared with the QW group. The primary efficacy analyses were performed using a modified intent-to-treat (MITT) population, defined as all patients meeting all inclusion/exclusion criteria (or, if not satisfying all criteria, were granted an exemption at study entry), and who were randomized and received at least one dose of study medication. A per-protocol population, based on all patients who met the MITT criteria and completed the entire study, was used to evaluate the robustness of the MITT results. Quality of life was assessed for all dosing groups throughout the study. Safety was based on all patients randomized who received at least one dose of study medication. Results A total of 519 patients were enrolled; 445 were included in the MITT population. The four treatment groups were comparable with respect to baseline characteristics. The primary etiologies of CKD were diabetes (45.7%) and hypertension (29.9%). The mean baseline Hb, serum creatinine and glomerular filtration rate for all patients were 11.9 +/- 0.8 g/dl, 3.1 mg/dl, and 21.1 ml/min/1.73 m2, respectively. The mean baseline transferrin saturation was 25.2% and the mean ferritin was 201.9 ng/ml for all patients. All groups had a mean final Hb of > 11.0 g/dl. The mean final Hb levels of the Q2W and Q4W groups were statistically non-inferior to the QW group. The results of the per-protocol analysis were consistent with the MITT results. In addition, 93.5%, 89.5%, 77.2%, and 76.0% of patients maintained a mean Hb > or = 11.0 g/dl throughout the course of the study in the QW, Q2W, Q3W, and Q4W groups, respectively. Quality of life was maintained or improved from baseline to final within each dosing group. There were no significant differences in the mean final quality of life scores between the QW group and the Q2W, Q3W, and Q4W groups. Among the 513 patients evaluated for safety, Epoetin Alfa was well tolerated with no differences in adverse events between groups. The incidence of thrombotic adverse events was low (2.5% of patients), as was mortality (1.4% of patients). Conclusions Approximately 90% of patients dosed once every two weeks and over 75% of patients dosed once every three or four weeks maintained mean Hb levels > or = 11.0 g/dl, consistent with the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. This study suggests that extended Epoetin Alfa dosing schedules are effective and safe for maintaining Hb, and may offer the possibility of increased flexibility and convenience for the majority of patients with the anemia of CKD.

  • once weekly Epoetin Alfa for treating the anemia of chronic kidney disease
    Clinical Nephrology, 2004
    Co-Authors: Robert Provenzano, L Garciamayol, P Suchinda, B Von Hartitzsch, S B Woollen, R Zabaneh, Jeffrey C Fink
    Abstract:

    Background and aim: Anemia occurs in approximately 47% of patients with chronic kidney disease (CKD) not on dialysis. Recombinant human erythropoietin (r-HuEPO, Epoetin Alfa) has been proven safe and effective for anemia treatment in patients with CKD using a three times-weekly regimen. The current study was conducted to evaluate the clinical safety and efficacy of a less frequent dosing regimen (once weekly) in this population. Methods: This prospective, multicenter, open-label, non-randomized study enrolled 1,557 adult anemic (hemoglobin (Hb) ≤10 g/dl) CKD patients not on dialysis. Epoetin Alfa 10,000 U was administered subcutaneously once weekly for 16 weeks. Titration to 20,000 U once weekly at week 5 was permitted if patients had an increase in Hb < 1 g/dl. Safety and efficacy were assessed by changes in health-related quality of life (Linear Analog Scale Assessment (LASA) and Kidney Disease Questionnaire (KDQ)), changes in hematologic parameters and transfusion utilization, and incidence and severity of adverse events. Results: 1,338 patients were evaluable for efficacy. Mean Hb level increased from 9.1 g/dl at baseline to 11.6 g/dl at study completion (last observed value after baseline) (p < 0.0001). Overall, 89.8% of patients responded to once-weekly dosing, exhibiting an increase in Hb level of ≥ 1 g/dl from baseline. The percentage of patients that required transfusion decreased from 11.1% (baseline) to 3.7% (during the study) (p < 0.0001). All quality-of-life parameters improved significantly from baseline (p < 0.0001). Mean LASA scores for energy, activity and overall quality of life increased from baseline to study completion by 27.9 mm (70.5%), 24.5 mm (57.0%) and 22.6 mm (47.4%), respectively. All 5 KDQ domains showed statistically significant improvements (p < 0.0001). Hb change was a strong predictor for all 5 KDQ domains and the overall score (p < 0.0001). Treatment with once-weekly Epoetin Alfa was well tolerated, similar to that reported with three times-weekly dosing. Conclusion: Once-weekly Epoetin Alfa therapy is safe and effective for treating anemia in patients with CKD not on dialysis, and is associated with significant improvements in functional status and quality of life.

  • Epoetin Alfa clinical evolution of a pleiotropic cytokine
    JAMA Internal Medicine, 2004
    Co-Authors: David H Henry, Peter M Bowers, Michael T Romano, Robert Provenzano
    Abstract:

    Recombinant human erythropoietin (Epoetin Alfa) has been used in clinical settings for more than a decade. Its indications have expanded considerably from its original use as hormone therapy in the treatment of anemia in adults with chronic kidney disease. Since the introduction of Epoetin Alfa, a greater understanding of anemia pathophysiology and the interactions of erythropoietin, iron, and erythropoiesis has been elucidated. Anemia is now independently associated with increased mortality and disease progression. Potential survival benefits associated with correction of anemia in various patient populations are leading to consideration of earlier, more aggressive treatment of mild to moderate anemia with Epoetin Alfa. Moreover, this agent's therapeutic use may extend beyond currently accepted roles. Epoetin Alfa is undergoing evaluation with promising results in a variety of new clinical settings, including anemia associated with congestive heart failure, ribavirin-interferon Alfa treatment of hepatitis C virus infection, and critical illness. Preclinical studies also have established erythropoietin and its recombinant equivalent to be a pleiotropic cytokine with antiapoptotic activity and neuroprotective actions in the central nervous system. The therapeutic potential of Epoetin Alfa appears yet to be fully realized.

Lynda A Szczech - One of the best experts on this subject based on the ideXlab platform.

  • roxadustat fg 4592 versus Epoetin Alfa for anemia in patients receiving maintenance hemodialysis a phase 2 randomized 6 to 19 week open label active comparator dose ranging safety and exploratory efficacy study
    American Journal of Kidney Diseases, 2016
    Co-Authors: Robert Provenzano, Anatole Besarab, Steven Wright, Steven Zeig, Peter Nguyen, Lona Poole, Khalil G Saikali, Gopal Saha, Stefan Hemmerich, Lynda A Szczech
    Abstract:

    Background Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. Study Design Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. Setting & Participants Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with Epoetin Alfa. Intervention Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous Epoetin Alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of Epoetin Alfa responsiveness. Intravenous iron was prohibited. Outcomes Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of −0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). Measurements Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). Results Baseline Epoetin Alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and Epoetin Alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the Epoetin Alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus Epoetin Alfa (P Limitations Short treatment duration and small sample size. Conclusions In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels.

  • correction of anemia with Epoetin Alfa in chronic kidney disease
    The New England Journal of Medicine, 2006
    Co-Authors: Ajay K Singh, Marsha Wolfson, Lynda A Szczech, Kezhen L Tang, Huiman X Barnhart, Shelly K Sapp, Donal N Reddan, Abstr Act
    Abstract:

    Background Anemia, a common complication of chronic kidney disease, usually develops as a consequence of erythropoietin deficiency. Recombinant human erythropoietin (Epoetin Alfa) is indicated for the correction of anemia associated with this condition. However, the optimal level of hemoglobin correction is not defined. Methods In this open-label trial, we studied 1432 patients with chronic kidney disease, 715 of whom were randomly assigned to receive a dose of Epoetin Alfa targeted to achieve a hemoglobin level of 13.5 g per deciliter and 717 of whom were assigned to receive a dose targeted to achieve a level of 11.3 g per deciliter. The median study duration was 16 months. The primary end point was a composite of death, myocardial infarction, hospitalization for congestive heart failure (without renal replacement therapy), and stroke. Results A total of 222 composite events occurred: 125 events in the high-hemoglobin group, as compared with 97 events in the low-hemoglobin group (hazard ratio, 1.34; 95% confidence interval, 1.03 to 1.74; P = 0.03). There were 65 deaths (29.3%), 101 hospitalizations for congestive heart failure (45.5%), 25 myocardial infarctions (11.3%), and 23 strokes (10.4%). Seven patients (3.2%) were hospitalized for congestive heart failure and myocardial infarction combined, and one patient (0.5%) died after having a stroke. Improvements in the quality of life were similar in the two groups. More patients in the high-hemoglobin group had at least one serious adverse event. Conclusions The use of a target hemoglobin level of 13.5 g per deciliter (as compared with 11.3 g per deciliter) was associated with increased risk and no incremental improvement in the quality of life. (ClinicalTrials.gov number, NCT00211120.)

Jeffrey Crawford - One of the best experts on this subject based on the ideXlab platform.

  • a randomized trial comparing immediate versus delayed treatment of anemia with once weekly Epoetin Alfa in patients with non small cell lung cancer scheduled to receive first line chemotherapy
    Journal of Thoracic Oncology, 2007
    Co-Authors: Jeffrey Crawford, Francisco Robert, Michael C Perry, Chandra P Belani, Denise Williams
    Abstract:

    Introduction: This study evaluated the safety/efficacy of once-weekly (QW) Epoetin Alfa measured by quality of life (QOL), hemoglobin (Hb), transfusion incidence, tumor response, and survival in patients with chemotherapy-naive, advanced non-small cell lung cancer (NSCLC). Methods: Stage IIIB/IV NSCLC patients with Hb ≥11 to Results: The study was terminated early because of slow accrual; of 216 patients enrolled, 211 were evaluable for efficacy. Hb was maintained in the immediate group, but it decreased in the delayed group (12.9 versus 11.6 g/dl final values, respectively). Numerically, fewer immediate patients required transfusions versus delayed patients. Mean QOL scores, modestly declining in both groups from baseline to final measurement, were not significantly different between groups. Tumor response and median overall survival were similar between groups. Epoetin Alfa was well tolerated, with a similar thrombovascular event rate between groups. Conclusion: Epoetin Alfa in subcutaneous doses of 40,000 U QW, given immediately at chemotherapy initiation for advanced NSCLC, was well tolerated, and it effectively maintained Hb, leading to a reduced transfusion incidence versus delayed Epoetin Alfa. Overall QOL scores were higher than typical in this population, decreasing slightly during treatment in both groups. Overall survival was similar between groups, with no evidence of a negative effect by early Epoetin Alfa intervention.

  • clinical benefits of Epoetin Alfa therapy in patients with lung cancer
    Clinical Lung Cancer, 2002
    Co-Authors: Jeffrey Crawford, George D Demetri, Janice L Gabrilove, Michail V Blasi, Brenda Sarokhan, John A Glaspy
    Abstract:

    A retrospective subset analysis of anemic lung cancer patients who participated in three large, multicenter, community-based studies of 3-times-weekly (TIW) or once-weekly (QW) recombinant human erythropoietin (r-HuEPO, Epoetin Alfa) as an adjunct to chemotherapy was conducted. Patients were treated with Epoetin Alfa 150 U/kg in the first TIW study and with 10,000 U subcutaneously in the other study, with doubling of the dose if hemoglobin (Hb) response was inadequate. Patients in the QW study received Epoetin Alfa 40,000 U subcutaneously, which could be increased to 60,000 U. The maximum treatment duration for all three studies was 16 weeks. A total of 1748 lung cancer patients were evaluable for hematopoietic response; 1298 were evaluable for analyses of energy and 1300 were evaluable for analyses of activity and overall quality of life (QOL), as measured by the linear analogue scale assessment (LASA). Within 2 months of therapy, TIW and QW Epoetin Alfa therapy resulted in significant increases in Hb levels, decreases in transfusion requirements, and improvements in self-reported LASA scores. Increased Hb levels and reduced transfusion rates were demonstrated in the individual studies and in the analysis of data pooled from all three studies. Improvements in QOL parameters were significantly correlated with increased Hb levels. Epoetin Alfa was well tolerated in all studies. The clinical benefits and safety profiles of the TIW and the QW schedules appear to be similar. In addition, the QW schedule provides greater convenience to patients and physicians alike. Given the high incidence of anemia and transfusion utilization in patients presenting with lung cancer, Epoetin Alfa is an effective strategy for correcting anemia in these patients, thereby improving their energy levels, activity levels, and overall QOL.