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Increased Importance of Intravenous Iron in Chemotherapy-Induced Anemia

Department of Medicine, Georgetown University, Washington, DC

David H. Henry

Department of Medicine, University of Pennsylvania, Philadelphia, PA

To the Editor:

In the aftermath of the recent proscription against erythropoietic stimulatory agent (ESA) use in patients with hemoglobin levels higher than 120 G/L and in anemia of cancer patients not on chemotherapy, hematologists and oncologists are resetting their practice guidelines for these agents that have so positively impacted our patient care. Although many criticize the studies being imbalanced against the ESA treatment arms, we all must take heed of the implication that ESAs stimulate tumor growth. Nevermore has there been a need to ensure that adequate iron is available when ESAs are used. There are three published articles^1-3 and one presented abstract⁴ that all document an improved hemoglobin response and decreased exposure to ESAs needed to reach target hemoglobin levels when intravenous iron is supplied. The latter showed a statistically significantly decreased number of transfusions in the intravenous iron arm. Similar improvements were not seen when oral iron was used. The observed synergy between ESAs and intravenous iron was independent of baseline iron parameters including serum ferritin, percent transferrin saturation,^1,2 and stainable marrow hemosiderin.³ This is not surprising given the recent description of the iron regulatory protein, hepcidin, which inhibits iron availability and absorption and is upregulated in cancer and inflammatory states. Now that there are three safe intravenous iron preparations—low molecular weight iron dextran, ferric gluconate, and iron sucrose—the resistance to intravenous iron use in oncology patients receiving ESAs needs to be re-examined in order to maximize the efficiency of a therapy that will now come under markedly increased scrutiny.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author or immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment: N/A Leadership: N/A Consultant: Michael Auerbach, Watson Laboratories; David H. Henry, Watson Laboratories Stock: N/A Honoraria: Michael Auerbach, Fallon Medica Research Funds: David H. Henry, Watson Laboratories Testimony: N/A Other: N/A

REFERENCES

1. Auerbach M, Ballard H, Trout JR, et al: Intravenous iron optimizes the response to recombinant erythropoietin in cancer patients with chemotherapy-related anemia: A multicenter, open-label, randomized trial. J Clin Oncol 22: 1301-1307, 2004[Abstract/Free Full Text]

2. Henry DH, Dahl NV, Auerbach M, et al: Intravenous ferric gluconate significantly improves response to epoietin alpha versus oral iron and no iron in anemic patients with cancer receiving chemotherapy. The Oncologist 12: 231-242, 2007[Abstract/Free Full Text]

3. Hedenus M, Birgegard G, Nasman P, et al: Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: A randomized multicenter study. Leukemia [e-pub ahead of print January 25, 2007]

4. Lerchenmueller C, Husseini F, Gaede B, et al: Intravenous iron supplementation in patients with chemotherapy-induced anemia receiving darbepoietin alfa every three weeks: Iron parameters in a randomized controlled trial. Blood 108: 445, 2006 (abstr 1552)

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