Epoetin Treatment of Anemia Associated With Cancer Therapy: a Systematic Review and Meta-analysis of Controlled Clinical Trials

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.

Prognostic impact of hemoglobin levels on treatment outcome in patients with nasopharyngeal carcinoma treated with sequential chemoradiotherapy or radiotherapy alone

“…Phase I/II and randomized trials have demonstrated the beneficial effects of this option in improving Hb levels in patients with malignant disease, with rapid and pronounced responses having been observed. 29 The use of erythropoietin in patients receiving radiotherapy or chemoradiotherapy has been examined only recently, 30 -34 and it remains uncertain whether such an approach will improve treatment outcome. In fact, a recent randomized trial reported poorer locoregional control in patients randomized to receive erythropoietin during radiotherapy.…”

Managing chemotherapy induced anemia with darbepoetin alfa and other erythropoiesis stimulating agents: a nurse's perspective

“…Both epoetin alfa and epoetin beta have been shown to be effective in correcting Hb levels and to reduce the need for RBC transfusions compared with placebo in several randomized clinical trials. 13 The recommended dose frequency for epoetin alfa and epoetin beta was three times per week (TIW).…”

Are there clinical benefits with early erythropoietic intervention for chemotherapy‐induced anemia?

“…7 To determine whether these early observations were substantiated by subsequent studies, and to evaluate whether there now exists a substantial body of evidence in favor of early intervention, we included these studies in our analysis, in addition to the five studies we identified using our search criteria. 10,20,24,27,30 Transfusion outcome Table 2 summarizes the transfusion outcomes of all seven studies.…”

“…5 Clinical practice guidelines for the management of CIA, issued jointly by the American Society of Clinical Oncology (ASCO) and the American Society of Hematology (ASH), 6 have recommended the use of erythropoietic agents in patients with hemoglobin Յ 10 g/dL. These recommendations were based on a systematic review of the literature (from 1985 to 1999) on the effectiveness of erythropoietic proteins for the treatment of CIA that included 22 randomized controlled trials (RCTs) in 1927 patients 7 (Table 1). In contrast, the guidelines made no definitive recommendation for patients with Grade 1 anemia.…”