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Journal of Clinical Oncology, Vol 22, No 21 (November 1), 2004: pp. 4428 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.04.860
Iron Supplement in Cancer Patients Receiving ErythropoietinDivisione di Oncologia Medica Falck, Ospedale Niguarda Ca' Granda, Milano, Italy To the Editor: Auerbach et al1 report on a randomized trial of iron supplement in cancer patients with chemotherapy-related anemia receiving recombinant human erythropoietin (rHuEPO). This study is important, because in previous clinical trials of rHuEPO, iron usage has never been energetically pursued in cancer patients and its use has been generally left to the discretion of the individual investigator. We would like to make the following remarks about the Auerbach et al trial for better interpretation of results. (1) Criteria for defining absolute or functional iron deficiency adopted by the authors should be detailed, as there is not concordance in the literature about this point2; (2) the fraction of patients with absolute iron deficiency within the four study groups should be specified. Because of absence of iron stores, in this subset of patients, it is clinically cautious to postpone treatment with erythropoietic agents until iron stores are replenished or to treat iron deficiency aggressively along with rHuEPO therapy. In the same circumstances, administration of rHuEPO alone would be pathophysiologic nonsense.3 When functional iron deficiency is present in patients receiving rHuEPO, iron repletion is already recommended based on indirect evidence and biologic inferences as literally stated in the American Society of Clinical Oncology/American Society of Hematology guidelines.4 The study by Auerbach et al1 addresses this issue in a controlled trial for the first time and confirms that iron supplement should be given intravenously rather then orally, as the latter is shown largely ineffective in cancer patients as it also occurs in the setting of anemia in other chronic diseases.5 A major point that remains to be elucidated in the field of rHuEPO therapy for anemia of cancer is whether iron supplement is capable of increasing the fraction of patients without iron deficiency responding to erythropoietic agents. Owing to the increased erythropoietic activity stimulated by rHuEPO, adequate delivery of iron to the bone marrow from the beginning of rHuEPO therapy may well optimize response in these patients as well (ie, by avoiding the development of iron deficiency, whose occurrence during rHuEPO therapy represents a major limitation to its efficacy).2 This important point should be addressed in future prospective trials. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Auerbach M, Ballard H, Trout JR, et al: Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: A multicenter, open label, randomized trial. J Clin Oncol 22:1301-1307, 2004
2. Beguin Y: Prediction of response and other improvements on the limitations of recombinant human erythropoietin therapy in anemic cancer patients. Haematologica 87:1209-1221, 2002
3. Goodnough LT, Skikne B, Brugnara C: Erythropoietin, iron, and erythropoiesis. Blood 96:823-833, 2000
4. Rizzo J, Lichtin AE, Woolf SH, et al: Use of epoietin in patients with cancer: Evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol 20:4083-4107, 2002 5. Kosch M, Schaefer RM: Iron management in renal failure patients-how do we achieve the best results? EDTNA ERCA J 28:182-184, 2002[Medline]
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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