Ursula Matulonis, MD
Do erythropoiesis-stimulating agents (ESAs) used for prevention or treatment of anemia increase mortality in patients with cancer?
Included studies compared ESAs (epoetin or darbepoetin) plus red blood cell (RBC) transfusions as needed with RBC transfusions as needed alone for prevention or treatment of anemia in patients with cancer. Exclusion criteria were trials of high-dose myeloablative chemotherapy plus stem-cell transplantation, those with planned sample sizes of < 100 patients or analyses including < 50 patients, or in which > 20% of patients had myelodysplastic syndromes or acute leukemia or used ESAs as preoperative treatment. Outcomes were mortality during active study periods (≤ 28 d after end of period) and overall survival during follow-up.
MEDLINE, EMBASE/Excerpta Medica, Cochrane Library, and conference proceedings (1985 to Jan 2008) were searched for randomized controlled trials (RCTs). Manufacturers of ESAs and trialists were contacted. Individual patient data were obtained and pooled. 53 RCTs (n = 13 933 eligible for analysis, 63% women, 58% metastatic or advanced cancer) met selection criteria and had sufficient data for analysis: 38 with chemotherapy, 3 with radiotherapy, and 5 with concurrent radiation and chemotherapy. 37 RCTs were completed, 14 were stopped prematurely, and 2 were in progress.
Median follow-up was 4 months during the active study period and 6 to 8 months overall. Meta-analysis showed that ESAs increased mortality during the active study period; the reduction in survival associated with ESAs during longer follow-up was of borderline statistical significance (Table). Meta-analysis showed similar effects in the subset of chemotherapy trials, but these were not statistically significant (Table).
Erythropoiesis-stimulating agents increase mortality in patients who have cancer and anemia or potential for anemia.
Erythropoiesis-stimulating agents, with or without red blood cell transfusions (RBCTs), vs RBCTs as needed in patients with cancer*
*NS = not significant; other abbreviations defined in Glossary. Weighted event rates, RRI, NNH, and CI calculated from data in article using a fixed-effect model.
†Estimated without adjustment for length of follow-up.
‡Calculated using data provided by author.
Matulonis U. Review: Erythropoiesis-stimulating agents increase mortality in patients with cancer. Ann Intern Med. ;151:JC3–7. doi: 10.7326/0003-4819-151-6-200909150-02007
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Published: Ann Intern Med. 2009;151(6):JC3-7.
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