A Randomized Controlled Trial of Darbepoetin Alfa Administered as a Fixed or Weight-Based Dose Using a Front-Loading Schedule in Patients with Anemia Who Have Nonmyeloid Malignancies

Paul J. Hesketh, Francis Arena, Dhimant Patel, Matt Austin, Paul D'Avirro, Gregory Rossi, Alan Colowick, Lee Schwartzberg

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. The effect of using fixed versus weight-based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight-based dose using an accelerated correction and maintenance dosing regimen (front-loading). METHODS. During the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325 μg (n = 122) or at a weight-based dose of 4.5 μg/kg (n = 120) once weekly until they achieved a hemoglobin concentration ≥ 12.0 g/dL. Patients then received darbepoetin alfa (325 μg or 4.5 μg/kg) once every 3 weeks for the remainder of the 16-week treatment period (maintenance phase). RESULTS. Darbepoetin alfa resulted in high Kaplan-Meier rates of hematopoietic response (≥ 2 g/dL increase from the baseline level or a hemoglobin level ≥ 12 g/dL) in both the fixed-dose group (86% 95% confidence interval [95% CI], 78-94%) and the weight-based dose group (84%; 95% CI, 76-92%). The median time to hematopoietic response was 34 days (95% CI, 28-44 days) for the fixed-dose group and 36 days (95% CI, 30-45 days) for the weight-based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight-based doses were observed. CONCLUSIONS. Darbepoetin alfa was effective when administered as either a fixed dose or a weight-based dose using a front-loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease.

Original languageEnglish (US)
Pages (from-to)859-868
Number of pages10
JournalCancer
Volume100
Issue number4
DOIs
StatePublished - Feb 15 2004

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Anemia
Appointments and Schedules
Randomized Controlled Trials
Weights and Measures
Hemoglobins
Neoplasms
Confidence Intervals
Maintenance
Darbepoetin alfa
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

A Randomized Controlled Trial of Darbepoetin Alfa Administered as a Fixed or Weight-Based Dose Using a Front-Loading Schedule in Patients with Anemia Who Have Nonmyeloid Malignancies. / Hesketh, Paul J.; Arena, Francis; Patel, Dhimant; Austin, Matt; D'Avirro, Paul; Rossi, Gregory; Colowick, Alan; Schwartzberg, Lee.

In: Cancer, Vol. 100, No. 4, 15.02.2004, p. 859-868.

Research output: Contribution to journalArticle

Hesketh, Paul J. ; Arena, Francis ; Patel, Dhimant ; Austin, Matt ; D'Avirro, Paul ; Rossi, Gregory ; Colowick, Alan ; Schwartzberg, Lee. / A Randomized Controlled Trial of Darbepoetin Alfa Administered as a Fixed or Weight-Based Dose Using a Front-Loading Schedule in Patients with Anemia Who Have Nonmyeloid Malignancies. In: Cancer. 2004 ; Vol. 100, No. 4. pp. 859-868.
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title = "A Randomized Controlled Trial of Darbepoetin Alfa Administered as a Fixed or Weight-Based Dose Using a Front-Loading Schedule in Patients with Anemia Who Have Nonmyeloid Malignancies",
abstract = "BACKGROUND. The effect of using fixed versus weight-based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight-based dose using an accelerated correction and maintenance dosing regimen (front-loading). METHODS. During the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325 μg (n = 122) or at a weight-based dose of 4.5 μg/kg (n = 120) once weekly until they achieved a hemoglobin concentration ≥ 12.0 g/dL. Patients then received darbepoetin alfa (325 μg or 4.5 μg/kg) once every 3 weeks for the remainder of the 16-week treatment period (maintenance phase). RESULTS. Darbepoetin alfa resulted in high Kaplan-Meier rates of hematopoietic response (≥ 2 g/dL increase from the baseline level or a hemoglobin level ≥ 12 g/dL) in both the fixed-dose group (86{\%} 95{\%} confidence interval [95{\%} CI], 78-94{\%}) and the weight-based dose group (84{\%}; 95{\%} CI, 76-92{\%}). The median time to hematopoietic response was 34 days (95{\%} CI, 28-44 days) for the fixed-dose group and 36 days (95{\%} CI, 30-45 days) for the weight-based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight-based doses were observed. CONCLUSIONS. Darbepoetin alfa was effective when administered as either a fixed dose or a weight-based dose using a front-loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease.",
author = "Hesketh, {Paul J.} and Francis Arena and Dhimant Patel and Matt Austin and Paul D'Avirro and Gregory Rossi and Alan Colowick and Lee Schwartzberg",
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T1 - A Randomized Controlled Trial of Darbepoetin Alfa Administered as a Fixed or Weight-Based Dose Using a Front-Loading Schedule in Patients with Anemia Who Have Nonmyeloid Malignancies

AU - Hesketh, Paul J.

AU - Arena, Francis

AU - Patel, Dhimant

AU - Austin, Matt

AU - D'Avirro, Paul

AU - Rossi, Gregory

AU - Colowick, Alan

AU - Schwartzberg, Lee

PY - 2004/2/15

Y1 - 2004/2/15

N2 - BACKGROUND. The effect of using fixed versus weight-based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight-based dose using an accelerated correction and maintenance dosing regimen (front-loading). METHODS. During the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325 μg (n = 122) or at a weight-based dose of 4.5 μg/kg (n = 120) once weekly until they achieved a hemoglobin concentration ≥ 12.0 g/dL. Patients then received darbepoetin alfa (325 μg or 4.5 μg/kg) once every 3 weeks for the remainder of the 16-week treatment period (maintenance phase). RESULTS. Darbepoetin alfa resulted in high Kaplan-Meier rates of hematopoietic response (≥ 2 g/dL increase from the baseline level or a hemoglobin level ≥ 12 g/dL) in both the fixed-dose group (86% 95% confidence interval [95% CI], 78-94%) and the weight-based dose group (84%; 95% CI, 76-92%). The median time to hematopoietic response was 34 days (95% CI, 28-44 days) for the fixed-dose group and 36 days (95% CI, 30-45 days) for the weight-based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight-based doses were observed. CONCLUSIONS. Darbepoetin alfa was effective when administered as either a fixed dose or a weight-based dose using a front-loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease.

AB - BACKGROUND. The effect of using fixed versus weight-based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight-based dose using an accelerated correction and maintenance dosing regimen (front-loading). METHODS. During the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325 μg (n = 122) or at a weight-based dose of 4.5 μg/kg (n = 120) once weekly until they achieved a hemoglobin concentration ≥ 12.0 g/dL. Patients then received darbepoetin alfa (325 μg or 4.5 μg/kg) once every 3 weeks for the remainder of the 16-week treatment period (maintenance phase). RESULTS. Darbepoetin alfa resulted in high Kaplan-Meier rates of hematopoietic response (≥ 2 g/dL increase from the baseline level or a hemoglobin level ≥ 12 g/dL) in both the fixed-dose group (86% 95% confidence interval [95% CI], 78-94%) and the weight-based dose group (84%; 95% CI, 76-92%). The median time to hematopoietic response was 34 days (95% CI, 28-44 days) for the fixed-dose group and 36 days (95% CI, 30-45 days) for the weight-based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight-based doses were observed. CONCLUSIONS. Darbepoetin alfa was effective when administered as either a fixed dose or a weight-based dose using a front-loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease.

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