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Michael Auerbach and Harold Ballard

Edited by Kerrin G. Robinson

Intravenous iron (IV Fe) as an adjunct to therapy with erythropoiesis-stimulatory agents (ESAs) is standard care in dialysis-associated anemia, adding huge increments in hemoglobin and hematopoietic responses and decreased transfusions without significant toxicity. Cost savings, decreased exposure to ESAs, and decreased times to reach target hemoglobins are realized. Although similar benefits have been seen in all studies performed in patients with chemotherapy-induced anemia (CIA), experts are reluctant to incorporate routine use of IV Fe into treatment, largely because of misinterpretation and misunderstanding of the clinical nature of adverse events reportedly associated with its administration. IV Fe is therefore underused in oncology patients with anemia. Published experience with more than 1000 patients in clinical trials involving the use of IV Fe suggests minimal toxicity and substantial benefit are experienced when high molecular weight iron dextran is avoided. This article presents evidence recommending routine incorporation of IV Fe into treatment for CIA.

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Anat Gafter-Gvili, David P. Steensma and Michael Auerbach

Coadministration of intravenous (IV) iron improves responses to erythropoiesis-stimulating agents (ESAs) in the treatment of cancer-associated (CAA) and chemotherapy-induced anemia (CIA). Twelve prospective studies have demonstrated synergy between parenteral iron and ESAs, with variable degrees of improved hemoglobin (Hgb) response rates, shorter times to target Hgb levels, and a lower ESA dose required for equivalent Hgb responses. Clinically significant adverse events (AEs) with currently available IV iron products are uncommon. Pretreatment serum hepcidin levels may predict response magnitude. Safety concerns among many oncologists are driven by reports of serious AEs from older IV iron formulations that are no longer available, and misinterpretation of the nature and frequency of minor infusion reactions. Premedication with antihistamines is of unproven benefit and can cause symptoms that mimic anaphylaxis, prompting intervention with vasopressors and converting self-limited reactions into hemodynamically significant AEs. Payer rules proscribing the administration of ESAs and IV iron on the same day also have limited the clinical adoption of IV iron and ESA coadministration. At a time when financial resources are scarce, the ability to reduce use of costly ESAs is beneficial. Despite a favorable risk/benefit ratio for IV iron in CAA and CIA, current IV iron recommendations in guidelines from ASCO/ASH, NCCN, and ESMO are inconsistent. The authors believe more routine use of IV iron for CAA and CIA is appropriate in view of existing evidence, and suggest reconsideration of the current ASCO/ASH guidelines, which state “there is insufficient evidence to consider the use of intravenous iron as a standard of care.”