Epoetin treatment of anemia associated with cancer therapy: A systematic review and meta-analysis of controlled clinical trials

Jerome Seidenfeld, Margaret Piper, Carole Flamm, Victor Hasselblad, James Olen Armitage, Charles L. Bennett, Michael S. Gordon, Allan E. Lichtin, James L. Wade, Steven Woolf, Naomi Aronson

Research output: Contribution to journalReview article

201 Citations (Scopus)

Abstract

Epoetin treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this review is to facilitate more efficient use of epoetin by 1) quantifying the effects of epoetin on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia and 2) evaluating whether outcomes are superior when epoetin treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying studies. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized, controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized but unblinded trials and trials with excessive exclusions were included in the meta-analysis but were defined as lower quality. Twenty-two trials (n = 1927) met inclusion criteria, and 12 (n = 1390) could be combined for estimation of odds of transfusion. Epoetin decreased the percentage of patients transfused by 9%-45% in adults with mean baseline hemoglobin concentrations of 10 g/dL or less (seven trials; n = 1080), by 7%-47% in those with hemoglobin concentrations greater than 10 g/dL but less than 12 g/dL (seven trials; n = 431), and by 7%-39% in those with hemoglobin concentrations of 12 g/dL or higher (five trials; n = 308). In sensitivity analysis, the combined odds ratio for transfusion in epoetin-treated patients as compared with controls was 0.45 (95% confidence interval [CI] = 0.33 to 0.62) in higher quality studies and 0.14 (95% CI = 0.06 to 0.31) in lower quality studies. The number of patients needed to treat to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10 g/dL or less reported statistically significant effects of epoetin treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed epoetin's effects on anemia-related symptoms. We conclude that epoetin reduces the odds of transfusion for cancer patients undergoing therapy. Evidence is insufficient to determine whether initiating epoetin earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10 g/dL.

Original languageEnglish (US)
Pages (from-to)1204-1214
Number of pages11
JournalJournal of the National Cancer Institute
Volume93
Issue number16
DOIs
StatePublished - Aug 15 2001

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Second Primary Neoplasms
Controlled Clinical Trials
Meta-Analysis
Anemia
Hemoglobins
Quality of Life
Therapeutics
Confidence Intervals
Numbers Needed To Treat
Erythrocyte Transfusion
Randomized Controlled Trials
Odds Ratio
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Epoetin treatment of anemia associated with cancer therapy : A systematic review and meta-analysis of controlled clinical trials. / Seidenfeld, Jerome; Piper, Margaret; Flamm, Carole; Hasselblad, Victor; Armitage, James Olen; Bennett, Charles L.; Gordon, Michael S.; Lichtin, Allan E.; Wade, James L.; Woolf, Steven; Aronson, Naomi.

In: Journal of the National Cancer Institute, Vol. 93, No. 16, 15.08.2001, p. 1204-1214.

Research output: Contribution to journalReview article

Seidenfeld, J, Piper, M, Flamm, C, Hasselblad, V, Armitage, JO, Bennett, CL, Gordon, MS, Lichtin, AE, Wade, JL, Woolf, S & Aronson, N 2001, 'Epoetin treatment of anemia associated with cancer therapy: A systematic review and meta-analysis of controlled clinical trials', Journal of the National Cancer Institute, vol. 93, no. 16, pp. 1204-1214. https://doi.org/10.1093/jnci/93.16.1204
Seidenfeld, Jerome ; Piper, Margaret ; Flamm, Carole ; Hasselblad, Victor ; Armitage, James Olen ; Bennett, Charles L. ; Gordon, Michael S. ; Lichtin, Allan E. ; Wade, James L. ; Woolf, Steven ; Aronson, Naomi. / Epoetin treatment of anemia associated with cancer therapy : A systematic review and meta-analysis of controlled clinical trials. In: Journal of the National Cancer Institute. 2001 ; Vol. 93, No. 16. pp. 1204-1214.
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abstract = "Epoetin treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this review is to facilitate more efficient use of epoetin by 1) quantifying the effects of epoetin on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia and 2) evaluating whether outcomes are superior when epoetin treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying studies. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized, controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized but unblinded trials and trials with excessive exclusions were included in the meta-analysis but were defined as lower quality. Twenty-two trials (n = 1927) met inclusion criteria, and 12 (n = 1390) could be combined for estimation of odds of transfusion. Epoetin decreased the percentage of patients transfused by 9{\%}-45{\%} in adults with mean baseline hemoglobin concentrations of 10 g/dL or less (seven trials; n = 1080), by 7{\%}-47{\%} in those with hemoglobin concentrations greater than 10 g/dL but less than 12 g/dL (seven trials; n = 431), and by 7{\%}-39{\%} in those with hemoglobin concentrations of 12 g/dL or higher (five trials; n = 308). In sensitivity analysis, the combined odds ratio for transfusion in epoetin-treated patients as compared with controls was 0.45 (95{\%} confidence interval [CI] = 0.33 to 0.62) in higher quality studies and 0.14 (95{\%} CI = 0.06 to 0.31) in lower quality studies. The number of patients needed to treat to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10 g/dL or less reported statistically significant effects of epoetin treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed epoetin's effects on anemia-related symptoms. We conclude that epoetin reduces the odds of transfusion for cancer patients undergoing therapy. Evidence is insufficient to determine whether initiating epoetin earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10 g/dL.",
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AU - Hasselblad, Victor

AU - Armitage, James Olen

AU - Bennett, Charles L.

AU - Gordon, Michael S.

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AU - Woolf, Steven

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N2 - Epoetin treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this review is to facilitate more efficient use of epoetin by 1) quantifying the effects of epoetin on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia and 2) evaluating whether outcomes are superior when epoetin treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying studies. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized, controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized but unblinded trials and trials with excessive exclusions were included in the meta-analysis but were defined as lower quality. Twenty-two trials (n = 1927) met inclusion criteria, and 12 (n = 1390) could be combined for estimation of odds of transfusion. Epoetin decreased the percentage of patients transfused by 9%-45% in adults with mean baseline hemoglobin concentrations of 10 g/dL or less (seven trials; n = 1080), by 7%-47% in those with hemoglobin concentrations greater than 10 g/dL but less than 12 g/dL (seven trials; n = 431), and by 7%-39% in those with hemoglobin concentrations of 12 g/dL or higher (five trials; n = 308). In sensitivity analysis, the combined odds ratio for transfusion in epoetin-treated patients as compared with controls was 0.45 (95% confidence interval [CI] = 0.33 to 0.62) in higher quality studies and 0.14 (95% CI = 0.06 to 0.31) in lower quality studies. The number of patients needed to treat to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10 g/dL or less reported statistically significant effects of epoetin treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed epoetin's effects on anemia-related symptoms. We conclude that epoetin reduces the odds of transfusion for cancer patients undergoing therapy. Evidence is insufficient to determine whether initiating epoetin earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10 g/dL.

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