epoetin-alfa and Venous-Thrombosis

Erythropoiesis-stimulating proteins (ESPs) are indicated for the treatment of chemotherapy-induced anemia (CIA). Evidence-based guidelines and systematic reviews of the management of CIA do not yet include all currently approved ESPs or all of the clinically relevant benefits and risks of ESPs.. The aims of this work were to provide up-to-date assessments of the clinical efficacy and effectiveness (ie, transfusions and quality-of-life [QoL] benefits) and safety (ie, risk of venous thromboembolism [VTE] and all-cause or treatment-associated death) of epoetin-alfa, epoetin-beta, and darbepoetin-alfa for the treatment of CIA in cancer patients with hemoglobin<11 g/dL. We also considered the impact of differences in study design, patients, and treatments on the results.. A systematic review of the literature was performed to identify and analyze English-language studies (controlled trials and prospective uncontrolled studies with >or=300 patients) published between 1980 and July 2005. The databases searched were MEDLINE and the Cochrane Library. Relevant abstracts from the last 2 annual meetings of the American Society of Clinical Oncology, American Society of Hematology, and European Society for Medical Oncology were also included. Studies were selected, using predefined eligibility criteria. Two reviewers had to agree on all included and excluded studies, and on all data extracted from each accepted study before they were entered into a relational database. Meta-analyses were performed to quantify benefit and risk outcomes.. In total, 40 studies including 21,378 patients were eligible for analysis. Each ESP was found to have efficacy relative to standard care or placebo. The odds ratio (OR) for transfusions in studies of epoetin versus controls was 0.44 (95% CI, 0.35-0.55) and of darbepoetin versus controls was 0.41 (95% CI, 0.31-0.55). Patients receiving ESPs experienced a significant improvement in QoL; the mean difference in Functional Assessment of Cancer Therapy-Fatigue score for ESPs versus controls was 0.23 (95% CI, 0.10-0.36; P=0.001). The frequency of VTE and death was not significantly different between ESPs and control (VTE OR, 1.41 [95% CI, 0.81-2.47]; all-cause mortality OR, 1.00 [95% CI, 0.69-1.44]).. This analysis of key clinical benefits and risks of epoetin and darbepoetin in the treatment of CIA found no clinically relevant differences between these drugs.

Topics: Adult; Anemia; Antineoplastic Agents; Blood Transfusion; Child; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Quality of Life; Recombinant Proteins; Thromboembolism; Venous Thrombosis

Prospective, open-label, randomized, parallel-group study at 80 centers.. To demonstrate there is no clinically important additional risk for deep vein thrombosis with perioperative use of epoetin alfa versus standard of care in spine surgery without prophylactic anticoagulation.. Trials of epoetin alfa in orthopedic surgery that demonstrated no additional risk of thrombovascular events included perioperative pharmacologic anticoagulation.. Subjects received epoetin alfa 600 U/kg subcutaneously once weekly starting 3 weeks before spinal surgery plus standard of care for blood conservation, or standard of care alone. Perioperative anticoagulation therapy was not permitted; mechanical deep vein thrombosis prophylaxis was allowed. Doppler imaging for deep vein thrombosis was done on postoperative day 4 (or day of discharge), or for suspected deep vein thrombosis. Deep vein thrombosis was diagnosed by Doppler result or adverse event report. The criterion for no additional risk of deep vein thrombosis was a 1-sided 97.5% upper confidence limit < or =4% between groups.. Of the 680 subjects analyzed (340 in each treatment group), 16 (4.7%) in the epoetin alfa group and 7 (2.1%) in the standard of care group had a diagnosis of deep vein thrombosis either by Doppler or by adverse event report with normal Doppler. The between-group difference was 2.6% (97.5% upper confidence limit, 5.4%). Deep vein thrombosis confirmed by Doppler (4.1% vs. 2.1%), other clinically relevant thrombovascular events (1.5% vs. 0.9%), and all adverse events combined (76.5% vs. 73.2%) occurred with similar frequency in the 2 treatment groups.. This study documented a higher incidence of deep vein thrombosis and similar rates of other clinically relevant thrombovascular events with epoetin alfa versus standard of care for blood conservation in subjects who did not receive prophylactic anticoagulation before spinal surgery. Antithrombotic prophylaxis should be considered when erythropoietin is used in the surgical setting.

Topics: Aged; Anticoagulants; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Intention to Treat Analysis; Male; Middle Aged; Patient Selection; Perioperative Care; Prospective Studies; Recombinant Proteins; Spine; Ultrasonography, Doppler, Color; Venous Thrombosis

The optimum regimen of epoetin alfa for prevention of allogeneic blood transfusion is unknown.. To determine whether a modified regimen of epoetin alfa reduces allogeneic blood transfusion in patients undergoing hip arthroplasty.. Randomized, double-blind, multicenter trial comparing two modified dose regimens of epoetin alfa with placebo.. 13 teaching hospitals and 4 community hospitals in Canada.. 201 patients undergoing primary hip arthroplasty who had a hemoglobin concentration of 98 to 137 g/L and did not predonate blood.. Patients were assigned in a 3:5:5 ratio to receive four weekly doses of epoetin alfa, 40 000 U (high-dose; n = 44) or 20 000 U (low-dose; n = 79), or placebo (n = 78), starting 4 weeks before surgery. All patients received oral iron supplementation, 450 mg/d, for 42 or more days before surgery.. The primary end point was allogeneic transfusion. Secondary end points were thromboembolic events and change in reticulocyte count and hemoglobin concentration.. Both modified epoetin alfa regimens significantly reduced the need for allogeneic transfusion: Five (11.4%) patients in the high-dose group (P = 0.001) and 18 (22. 8%) patients in the low-dose group (P = 0.003) had transfusion, compared with 35 (44.9%) patients in the placebo group. The hematologic response was substantial in patients who received epoetin alfa. In the high-dose group, low-dose group, and placebo group, the preoperative increase in reticulocyte count was 58.8, 37. 0 and 1.8 x 10(9) cells/L (P < 0.001), respectively, and the increase in hemoglobin concentration was 19.5, 17.2, and 1.2 g/L (P < 0.001). The incidence of thromboembolic events did not differ among groups.. Both modified epoetin alfa regimens were effective compared with placebo in reducing allogeneic transfusion in patients undergoing hip arthroplasty. Patients who received high-dose epoetin alfa had the lowest transfusion rate.

Topics: Aged; Blood Transfusion; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobinometry; Humans; Iron; Male; Middle Aged; Patient Compliance; Polysaccharides; Pulmonary Embolism; Recombinant Proteins; Reticulocyte Count; Transfusion Reaction; Treatment Outcome; Venous Thrombosis

Recombinant epoetin alfa and darbepoetin alfa (r-HuEPO) have been shown to be safe and effective treatments for anemia, but recent reports have suggested an increased risk of thromboembolic events when these agents are used to treat chemotherapy-induced anemia among patients with breast or ovarian cancer. We examined the possible risk of such events among patients with ovarian or primary peritoneal carcinomas and chemotherapy-induced anemia.. We retrospectively analyzed data over 10 years from women at one hospital with ovarian or primary peritoneal carcinoma and chemotherapy-induced anemia. The incidence and odds ratio for development of deep venous thrombosis, unadjusted and adjusted for baseline differences and risk factors, was assessed between patients who had received r-HuEPO versus no treatment for anemia.. Of the 364 women, 90 had received r-HuEPO and 253 had not. The incidence of deep venous thrombosis was 6.7% in the group that had received r-HuEPO and 5.1% in the group that had not (unadjusted odds ratio, 1.31; 95% confidence interval [CI], 0.48-3.55). After adjustment for differences in age, body-mass index, prior thromboembolic disease or cancer, and tobacco use, the odds ratio for developing deep venous thrombosis with the use of r-HuEPO was 1.35 (95% CI, 0.49-3.75).. The use of r-HuEPO was not associated with an increased risk of deep venous thrombosis in this population. A randomized trial is needed to further explore this issue and to detail the safety and efficacy of these agents in patients with various other cancers.

Topics: Aged; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Recombinant Proteins; Venous Thrombosis

Topics: Cerebral Veins; Epoetin Alfa; Erythropoietin; Estrogen Antagonists; Hematinics; Humans; Recombinant Proteins; Tamoxifen; Venous Thrombosis