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For Cancer-Induced Anemia, ESAs Best Given With IV Iron

TOP - May 2014, Vol 7, No 2

About 50% of cancer patients —90% in some subsets—develop cancer- or chemotherapy-related anemia.1 For these patients, iron supplementation is a relatively safe and effective way to improve both hemoglobin level and quality of life, and it clearly enhances the effectiveness of erythropoiesis-stimulating agents (ESAs) in patients eligible to receive them, according to David Baribeault, BS, BCOP, clinical advisor for McKesson Health Solutions in the Pharmacy Optimization group.2

Baribeault made a case for intravenous (IV) iron supplementation in patients with cancer- and chemotherapy-induced anemia at the Hematology/Oncology Pharmacy Association 10th Annual Conference.

ESAs are effective for anemia related to cancer or chemotherapy—they reduce the need for transfusion and improve quality of life. However, 30% to 50% of patients do not achieve a clinically meaningful hematologic response,1 and restrictions imposed by the US Food and Drug Administration, due to safety concerns, have made ESAs more difficult to use, he said.

The reasons for nonresponse to ESAs are not clear, though actual or functional iron deficiency or a reduced reserve of stem cells in the bone marrow could be responsible. Even when patients respond, response may not occur for a month or longer. Transfusions are also effective, but they do carry some risk for infection, transfusion-related acute lung injury, and treatment-associated graft-versus-host disease.

“Though ESAs and transfusion can be used, we need to think of alternatives,” he said.

The best “alternative” is iron supplementation with 1 of 6 compounds on the market, the most recently approved being ferric carboxymaltose. The products have minor differences in terms of molecular weight, half-life, ability to be given as total-dose infusion, requirement of test dose, black box warning, and indications. In the future, these compounds will be joined by biosimilars.

Assessing Iron Deficiency
Iron status can be assessed 4 ways:

  • Serum iron, which measures iron available for hemoglobin synthesis (reference range, 60-150 µg/dL)
  • Total iron-binding capacity (TIBC; reference range, 250-435 µg/dL)
  • Transferrin iron saturation (TSAT), which also measures iron available for hemoglobin synthesis (reference range, 20%-50% in men, 15%-50% in women)
  • Serum ferritin, which is an indirect measure of total body iron stores (reference range, 20-250 ng/mL in men, 10-120 ng/mL in women).

A study by Henry and colleagues demonstrated that TSAT is the best predictor of iron deficiency in anemic cancer patients. In the study, 59% of patients had a TSAT value <20%, even if they had a serum ferritin level >100 ng/mL.1 Only 17% of patients had a serum ferritin level <100 ng/mL, but when ferritin was combined with TSAT, a large proportion of study patients were shown to have iron deficiency, he noted.

Adding Iron to ESAs
When erythropoietin is used to treat anemia caused by chemotherapy or other factors, functional iron deficiency ensues unless patients are iron-overloaded from prior transfusions. Iron therapy is therefore important in conjunction with ESAs, as it maximizes erythropoiesis by avoiding absolute and functional iron deficiency.

“Recent data indicate response may be improved by IV iron supplementation,” Baribeault stated.

A study by Auerbach and colleagues of patients receiving ESAs for chemotherapy-induced anemia showed a significant effect of adding IV iron (iron dextran): a mean change in hemoglobin of +2.5 g/dL over baseline and an improvement of +1.0 g/dL over oral iron.3 Administration by bolus and total-dose infusion was equally effective.

In another study by Henry and colleagues, IV sodium ferric gluconate complex (125 mg once a week) produced a significantly greater increase in hemoglobin and hemoglobin response (increase 2 g/dL) than did oral iron supplementation (ferrous sulfate 325 mg three times a day) or no iron.4 The mean increase in hemoglobin was 2.4 g/dL with IV iron, 1.6 g/dL with oral iron, and 1.5 g/dL when no iron was given.

A study by Bastit and colleagues showed that the addition of IV iron (sodium ferric gluconate complex in sucrose or iron sucrose) to darbepoetin alfa improved the hematopoietic response rate and reduced the need for transfusions from 20% to 9% over darbepoetin alone.5 In the same journal issue, Pedrazzoli and colleagues showed that patients with chemotherapy- related anemia and no iron deficiency (ie, replete by TSAT or ferritin levels) also were more likely to respond to darbepoetin when they received IV iron (sodium ferric gluconate).6

“This last study suggests that if you stimulate erythropoiesis, you have to include iron, even in patients who are iron replete,” Baribeault pointed out.

1. Henry DH, Dahl NV; on behalf of the Ferrlecit Cancer Study Group. Iron or vitamin B12 deficiency in anemic cancer patients prior to erythropoiesis-stimulating agent therapy. Commun Oncol. 2007;4(2):95-101.
2. Baribeault D. Cancer and chemotherapy-induced anemia: the roles of iron and ESAs. Presented at: 10th Annual Conference of the Hematology/Oncology Pharmacy Association; March 26-29, 2014; New Orleans, LA.
3. 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. 2004;22(7):1301-1307.
4. Henry DH, Dahl NV, Auerbach M, et al. Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy. Oncologist. 2007;12(2):231-242.
5. Bastit L, Vandebroek A, Altintas S, et al. Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. J Clin Oncol. 2008;26(10):1611-1618.
6. Pedrazzoli P, Farris A, Del Prete S, et al. Randomized trial of intravenous iron supplementation in patients with chemotherapy-related anemia without iron deficiency treated with darbepoetin alfa. J Clin Oncol. 2008;26(10):1619-1625.

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