Comparison of darbepoetin alfa dosed weekly (QW) vs. extended dosing schedule (EDS) in the treatment of anemia in patients receiving multicycle chemotherapy in a randomized, phase 2, open-label trial

Lee Schwartzberg, Ronald Burkes, Barry Mirtsching, Timothy Rearden, Peter T. Silberstein, Lorrin Yee, Amy Inamoto, Tom Lillie

Research output: Contribution to journalArticle

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Abstract

Background: Chemotherapy-induced anemia (CIA) is responsive to treatment with erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa. Administration of ESAs on a synchronous schedule with chemotherapy administration could benefit patients by reducing clinic visits and potentially enhancing on-time chemotherapy delivery. Methods: This phase 2, 25-week, open-label study evaluated the noninferiority of darbepoetin alfa administered weekly vs. as an extended dosing schedule (every 2 or 3 weeks) in patients with CIA. Patients were randomized 1:1 to an extended dosing schedule (EDS: darbepoetin alfa 300 ug Q2W if chemotherapy was QW, Q2W, or Q4W or darbepoetin alfa 500 ug Q3W if chemotherapy was Q3W) or weekly (150 ug QW regardless of chemotherapy schedule). Stratification factors included chemotherapy cycle length, screening hemoglobin (<10 g/dL vs. [greater than or equal to] 10 g/dL), and tumor type (lung/gynecological vs. other nonmyeloid malignancies). The primary endpoint was change in hemoglobin from baseline to Week 13. Results: Seven hundred fifty-two patients (374 QW patients; 378 EDS patients) received [greater than or equal to] 1 dose of darbepoetin alfa and were included in the analysis. Demographics and disease state were similar between groups. Seventy-one percent of patients in the EDS group and 76% in the QW group achieved the target hemoglobin of [greater than or equal to] 11.0 g/dL. There was a minimal difference in the primary endpoint of mean change in hemoglobin (baseline to Week 13) between the QW and the EDS groups (-0.04 g/dL; 95% confidence interval: -0.26, 0.17 g/dL). The upper limit of the 95% confidence interval was less than the prespecified limit of <0.75 g/dL, supporting noninferiority of the EDS dosing schedule. Reported adverse events were similar between groups. A slight increase in transfusions was reported in the QW group. Conclusion: Darbepoetin alfa, when administered synchronously with chemotherapy, on an EDS appears to be similarly efficacious to darbepoetin alfa weekly dosing with no unexpected adverse events. This study provides prospective data on how multiple dosing regimens available with darbepoetin alfa can be synchronized with chemotherapy administered across a range of dosing schedules.Trial registration: ClinicalTrials.gov Identifier NCT00144131.

Original languageEnglish
Pages (from-to)581
Number of pages1
JournalBMC Cancer
DOIs
StateAccepted/In press - Oct 25 2010

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Anemia
Appointments and Schedules
Drug Therapy
Hemoglobins
Therapeutics
Hematinics
Darbepoetin alfa
Confidence Intervals
Ambulatory Care
Neoplasms
Demography
Prospective Studies
Lung

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cancer Research
  • Oncology

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Comparison of darbepoetin alfa dosed weekly (QW) vs. extended dosing schedule (EDS) in the treatment of anemia in patients receiving multicycle chemotherapy in a randomized, phase 2, open-label trial. / Schwartzberg, Lee; Burkes, Ronald; Mirtsching, Barry; Rearden, Timothy; Silberstein, Peter T.; Yee, Lorrin; Inamoto, Amy; Lillie, Tom.

In: BMC Cancer, 25.10.2010, p. 581.

Research output: Contribution to journalArticle

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title = "Comparison of darbepoetin alfa dosed weekly (QW) vs. extended dosing schedule (EDS) in the treatment of anemia in patients receiving multicycle chemotherapy in a randomized, phase 2, open-label trial",
abstract = "Background: Chemotherapy-induced anemia (CIA) is responsive to treatment with erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa. Administration of ESAs on a synchronous schedule with chemotherapy administration could benefit patients by reducing clinic visits and potentially enhancing on-time chemotherapy delivery. Methods: This phase 2, 25-week, open-label study evaluated the noninferiority of darbepoetin alfa administered weekly vs. as an extended dosing schedule (every 2 or 3 weeks) in patients with CIA. Patients were randomized 1:1 to an extended dosing schedule (EDS: darbepoetin alfa 300 ug Q2W if chemotherapy was QW, Q2W, or Q4W or darbepoetin alfa 500 ug Q3W if chemotherapy was Q3W) or weekly (150 ug QW regardless of chemotherapy schedule). Stratification factors included chemotherapy cycle length, screening hemoglobin (<10 g/dL vs. [greater than or equal to] 10 g/dL), and tumor type (lung/gynecological vs. other nonmyeloid malignancies). The primary endpoint was change in hemoglobin from baseline to Week 13. Results: Seven hundred fifty-two patients (374 QW patients; 378 EDS patients) received [greater than or equal to] 1 dose of darbepoetin alfa and were included in the analysis. Demographics and disease state were similar between groups. Seventy-one percent of patients in the EDS group and 76{\%} in the QW group achieved the target hemoglobin of [greater than or equal to] 11.0 g/dL. There was a minimal difference in the primary endpoint of mean change in hemoglobin (baseline to Week 13) between the QW and the EDS groups (-0.04 g/dL; 95{\%} confidence interval: -0.26, 0.17 g/dL). The upper limit of the 95{\%} confidence interval was less than the prespecified limit of <0.75 g/dL, supporting noninferiority of the EDS dosing schedule. Reported adverse events were similar between groups. A slight increase in transfusions was reported in the QW group. Conclusion: Darbepoetin alfa, when administered synchronously with chemotherapy, on an EDS appears to be similarly efficacious to darbepoetin alfa weekly dosing with no unexpected adverse events. This study provides prospective data on how multiple dosing regimens available with darbepoetin alfa can be synchronized with chemotherapy administered across a range of dosing schedules.Trial registration: ClinicalTrials.gov Identifier NCT00144131.",
author = "Lee Schwartzberg and Ronald Burkes and Barry Mirtsching and Timothy Rearden and Silberstein, {Peter T.} and Lorrin Yee and Amy Inamoto and Tom Lillie",
year = "2010",
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day = "25",
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language = "English",
pages = "581",
journal = "BMC Cancer",
issn = "1471-2407",
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T1 - Comparison of darbepoetin alfa dosed weekly (QW) vs. extended dosing schedule (EDS) in the treatment of anemia in patients receiving multicycle chemotherapy in a randomized, phase 2, open-label trial

AU - Schwartzberg, Lee

AU - Burkes, Ronald

AU - Mirtsching, Barry

AU - Rearden, Timothy

AU - Silberstein, Peter T.

AU - Yee, Lorrin

AU - Inamoto, Amy

AU - Lillie, Tom

PY - 2010/10/25

Y1 - 2010/10/25

N2 - Background: Chemotherapy-induced anemia (CIA) is responsive to treatment with erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa. Administration of ESAs on a synchronous schedule with chemotherapy administration could benefit patients by reducing clinic visits and potentially enhancing on-time chemotherapy delivery. Methods: This phase 2, 25-week, open-label study evaluated the noninferiority of darbepoetin alfa administered weekly vs. as an extended dosing schedule (every 2 or 3 weeks) in patients with CIA. Patients were randomized 1:1 to an extended dosing schedule (EDS: darbepoetin alfa 300 ug Q2W if chemotherapy was QW, Q2W, or Q4W or darbepoetin alfa 500 ug Q3W if chemotherapy was Q3W) or weekly (150 ug QW regardless of chemotherapy schedule). Stratification factors included chemotherapy cycle length, screening hemoglobin (<10 g/dL vs. [greater than or equal to] 10 g/dL), and tumor type (lung/gynecological vs. other nonmyeloid malignancies). The primary endpoint was change in hemoglobin from baseline to Week 13. Results: Seven hundred fifty-two patients (374 QW patients; 378 EDS patients) received [greater than or equal to] 1 dose of darbepoetin alfa and were included in the analysis. Demographics and disease state were similar between groups. Seventy-one percent of patients in the EDS group and 76% in the QW group achieved the target hemoglobin of [greater than or equal to] 11.0 g/dL. There was a minimal difference in the primary endpoint of mean change in hemoglobin (baseline to Week 13) between the QW and the EDS groups (-0.04 g/dL; 95% confidence interval: -0.26, 0.17 g/dL). The upper limit of the 95% confidence interval was less than the prespecified limit of <0.75 g/dL, supporting noninferiority of the EDS dosing schedule. Reported adverse events were similar between groups. A slight increase in transfusions was reported in the QW group. Conclusion: Darbepoetin alfa, when administered synchronously with chemotherapy, on an EDS appears to be similarly efficacious to darbepoetin alfa weekly dosing with no unexpected adverse events. This study provides prospective data on how multiple dosing regimens available with darbepoetin alfa can be synchronized with chemotherapy administered across a range of dosing schedules.Trial registration: ClinicalTrials.gov Identifier NCT00144131.

AB - Background: Chemotherapy-induced anemia (CIA) is responsive to treatment with erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa. Administration of ESAs on a synchronous schedule with chemotherapy administration could benefit patients by reducing clinic visits and potentially enhancing on-time chemotherapy delivery. Methods: This phase 2, 25-week, open-label study evaluated the noninferiority of darbepoetin alfa administered weekly vs. as an extended dosing schedule (every 2 or 3 weeks) in patients with CIA. Patients were randomized 1:1 to an extended dosing schedule (EDS: darbepoetin alfa 300 ug Q2W if chemotherapy was QW, Q2W, or Q4W or darbepoetin alfa 500 ug Q3W if chemotherapy was Q3W) or weekly (150 ug QW regardless of chemotherapy schedule). Stratification factors included chemotherapy cycle length, screening hemoglobin (<10 g/dL vs. [greater than or equal to] 10 g/dL), and tumor type (lung/gynecological vs. other nonmyeloid malignancies). The primary endpoint was change in hemoglobin from baseline to Week 13. Results: Seven hundred fifty-two patients (374 QW patients; 378 EDS patients) received [greater than or equal to] 1 dose of darbepoetin alfa and were included in the analysis. Demographics and disease state were similar between groups. Seventy-one percent of patients in the EDS group and 76% in the QW group achieved the target hemoglobin of [greater than or equal to] 11.0 g/dL. There was a minimal difference in the primary endpoint of mean change in hemoglobin (baseline to Week 13) between the QW and the EDS groups (-0.04 g/dL; 95% confidence interval: -0.26, 0.17 g/dL). The upper limit of the 95% confidence interval was less than the prespecified limit of <0.75 g/dL, supporting noninferiority of the EDS dosing schedule. Reported adverse events were similar between groups. A slight increase in transfusions was reported in the QW group. Conclusion: Darbepoetin alfa, when administered synchronously with chemotherapy, on an EDS appears to be similarly efficacious to darbepoetin alfa weekly dosing with no unexpected adverse events. This study provides prospective data on how multiple dosing regimens available with darbepoetin alfa can be synchronized with chemotherapy administered across a range of dosing schedules.Trial registration: ClinicalTrials.gov Identifier NCT00144131.

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DO - 10.1186/1471-2407-10-581

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