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.
RCT Entities:
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.
Authors: Jean-Luc Canon; Johan Vansteenkiste; Michael Hedenus; Pere Gascon; Carsten Bokemeyer; Heinz Ludwig; Jan Vermorken; Jason Legg; Beatriz Pujol; Ken Bridges Journal: Med Oncol Date: 2011-11-13 Impact factor: 3.064
Authors: Sameer Doshi; Wojciech Krzyzanski; Susan Yue; Steven Elliott; Andrew Chow; Juan José Pérez-Ruixo Journal: Clin Pharmacokinet Date: 2013-12 Impact factor: 6.447
Authors: Richard de Boer; Michael Clemens; Gabor Renczes; Dusan Kotasek; Jana Prausova; Norbert Marschner; Michael Hedenus; Sameer Doshi; Lisa Hendricks; Anders C Österborg Journal: Med Oncol Date: 2010-10-29 Impact factor: 3.064
Authors: Vicente Alberola Candel; Alfredo Carrato Mena; Eduardo Díaz-Rubio García; Pere Gascón Vilaplana; Manuel González Barón; Miguel Martín Jiménez; Emilio Alba Conejo; Javier Cassinello Espinosa; Ramon Colomer; Juan Jesús Cruz Hernández; Agustí Barnadas i Molins; Carlos Camps Herrero; Ana Ma Casas Fernández de Tejerina; Joan Carulla Torrent; Manuel Constenla Figueiras; Joaquin Gavilá Gregori; Ma Dolores Isla Casado; Bartomeu Massuti Sureda; Mariano Provencio Pulla; César Augusto Rodríguez Sánchez; Jaime Sanz Ortiz Journal: Clin Transl Oncol Date: 2009-11 Impact factor: 3.405
Authors: Thomas Thomaidis; Arndt Weinmann; Martin Sprinzl; Stephan Kanzler; Jochen Raedle; Matthias Ebert; Carl Cristoph Schimanski; Peter Robert Galle; Thomas Hoehler; Markus Moehler Journal: Int J Clin Oncol Date: 2013-03-27 Impact factor: 3.402
Authors: Lee Schwartzberg; Ronald Burkes; Barry Mirtsching; Timothy Rearden; Peter Silberstein; Lorrin Yee; Amy Inamoto; Tom Lillie Journal: BMC Cancer Date: 2010-10-25 Impact factor: 4.430
Authors: Johan Vansteenkiste; Michael Hedenus; Pere Gascon; Carsten Bokemeyer; Heinz Ludwig; Jan Vermorken; Lisa Hamilton; Ken Bridges; Beatriz Pujol Journal: BMC Cancer Date: 2009-09-03 Impact factor: 4.430