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JNCI Journal of the National Cancer Institute 2001 93(16):1204-1214; doi:10.1093/jnci/93.16.1204
© 2001 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 93, No. 16, 1204-1214, August 15, 2001
© 2001 Oxford University Press


REVIEW

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 O. Armitage, Charles L. Bennett, Michael S. Gordon, Allan E. Lichtin, James L. Wade, III, Steven Woolf, Naomi Aronson

Affiliations of authors: J. Seidenfeld, M. Piper, C. Flamm, N. Aronson, Technology Evaluation Center, Blue Cross and Blue Shield Association, Chicago, IL; V. Hasselblad, Duke University, Durham, NC; J. O. Armitage, University of Nebraska Medical Center, Omaha; C. L. Bennett, Department of Veterans Affairs Chicago Healthcare System/Lakeside Division and Northwestern University, Chicago, IL; M. S. Gordon, University of Arizona College of Medicine, Phoenix Campus; A. E. Lichtin, Cleveland Clinic Foundation, OH; J. L. Wade III, Cancer Care Specialists, Decatur, IL; S. Woolf, Medical College of Virginia, Richmond.

Correspondence to: Jerome Seidenfeld, Ph.D., Technology Evaluation Center, Blue Cross and Blue Shield Association, 225 North Michigan Ave., Chicago, IL 60601–7680 (e-mail: jerome.seidenfeld{at}bcbsa.com).

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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