Recent guidance from the Centers for Medicare and Medicaid Services restricting erythropoiesis-stimulating agents (ESAs) in chemotherapy and cancer-related anemias has resulted in an increase in transfusions. Nine studies, without published contradictory evidence, have shown optimization of the response to ESAs by intravenous (IV) iron when the iron was added to the treatment of chemotherapy-induced anemia. The synergy observed, although greater in iron deficiency, was independent of pretreatment iron parameters. Three studies demonstrated decreased transfusions when IV iron is administered without ESAs. Discordant recommendations regarding IV iron currently exist among the American Society of Hematology/American Society of Clinical Oncology guidelines, the National Comprehensive Cancer Network, and the European Society of Medical Oncology. This discordance is at least partly the result of misconceptions about the clinical nature and incidence of adverse effects with IV iron. Other reasons for this discordance are presented in this review. Based on thousands of studied patients, we conclude that IV iron is safe and probably safer than most physicians realize. Education is needed relating to the interpretation of minor, subclinical infusion reactions that resolve without therapy. IV iron without ESAs may be an effective treatment for chemotherapy-induced anemia and warrants further study. We present evidence supporting the conclusion that baseline serum hepcidin levels may predict responses to IV iron, and we examine the published evidence supporting the conclusion that IV iron should be a standard addition to the management of chemotherapy and cancer-related anemia.
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