Parenteral Iron for Cancer-Associated Anemia

Abstract & Commentary

By William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC. This article originally appeared in the March 2013 issue of Clinical Oncology Alert. It was peer reviewed by V.R. Veerapalli, MD. Dr. Veerapalli is Staff Clinician, INOVA Fairfax Cancer Center, Falls Church, VA. Drs. Ershler and Veerapalli report no financial relationships relevant to this field of study.

Synopsis: In an observational study conducted in Germany of more than 600 anemic cancer patients receiving parenteral iron (ferric carboxymaltose), hemoglobin levels were shown to rise significantly. The iron treatment was well tolerated. Randomized interventional studies are warranted to demonstrate efficacy in terms of physical function and quality of life and safety in this population.

Source: Steinmetz T, et al. Clinical experience with ferric carboxymaltose in the treatment of cancer- and chemotherapy-associated anemia. Ann Oncol 2013;24:475-482.

Anemia is common in cancer patients for a number of reasons, including iron deficiency, inflammation, and chemotherapy,1 and its presence negatively influences performance, quality of life, and even the effectiveness of tumor-directed therapy.2,3 In fact, iron deficiency even in the absence of anemia is associated with impaired physical function, weakness, and fatigue,4,5 all of which have been demonstrated to improve with iron supplementation.6,7

Iron deficiency can be recognized as either an absolute deficiency in total iron stores (low serum iron and ferritin levels) or by a reduction in utilizable iron in an individual with adequate stores (low transferrin saturation). Inasmuch as ferritin is upregulated during inflammation, the reliance on this measure may be misleading in patients with malignancy.

Anemia associated with cancer and cancer chemotherapy has been treated with erythropoiesis-stimulating agents (ESA) or red cell transfusions, but not infrequent adverse consequences have been reported and alternative approaches are under active investigation. In this light, intravenous iron, known to improve response to ESAs, may alone be an effective means of improving cancer-associated anemia, although the data on its use without coadministration of ESA are lacking. To address this, Steinmetz and colleagues evaluated effectiveness and tolerability of a commonly used (in Europe) parenteral iron preparation, ferric carboxymaltose (FCM), in the routine treatment of anemic cancer patients.

For the purposes of this observational review, data on 639 patients enrolled in 68 hematology/oncology practices throughout Germany were analyzed. Of the 639 patients, 619 received FCM at the oncologist’s discretion, 420 had eligible baseline hemoglobin (Hb) measurements, and 364 had at least one follow-up Hb measurement. Data of transfused patients were censored from analysis before transfusion.

The median total iron dose was 1000 mg per patient (interquartile range 600-1500 mg). The median Hb increase was comparable in patients receiving FCM alone (1.4 g/dL [0.2-2.3 g/dL; n = 233]) or FCM + ESA (1.6 g/dL [0.7-2.4 g/dL; n = 46]). Patients with baseline Hb up to 11.0 g/dL and serum ferritin up to 500 ng/mL benefited from FCM treatment (stable Hb ≥ 11.0 g/dL). Also, patients with ferritin > 500 ng/mL but low transferrin saturation benefited from FCM treatment. FCM was well tolerated; 2.3% of patients reported putative drug-related adverse events and these were mainly gastrointestinal. Only one serious adverse drug reaction occurred and this was in a heavily pretreated man with a head/neck tumor and pulmonary metastases who experienced respiratory failure on the same day he received his second FCM injection.

Commentary

Fatigue is a common occurrence among cancer patients, particularly those who are undergoing chemotherapy or radiation therapy. Although anemia is commonly observed, clinicians have been less aggressive about treating with ESAs or transfusion in patients with moderate anemia for fear of accelerating disease or shortening survival.8,9

Yet, there are studies now demonstrating efficacy of parenteral iron in improving hemoglobin levels and reducing transfusion requirements,10,11 and this, with the current observational analysis indicating both safety and efficacy of such an approach on a larger scale and in a variety of practice settings, provides rationale for more extensive investigation. In this regard, an interventional trial in cancer patients with mild-to-moderate anemia in which outcomes other than hemoglobin level, such as physical function (e.g., 6-minute walk test) and quality of life, would be very instructive.

References

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3. Thomas G. The effect of hemoglobin level on radiotherapy outcomes: The Canadian experience. Semin Oncol 2001;28(2 Suppl 8):60-65.

4. Brownlie TT, et al. Tissue iron deficiency without anemia impairs adaptation in endurance capacity after aerobic training in previously untrained women. Am J Clin Nutr 2004;79:437-443.

5. Krayenbuehl PA, et al. Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration. Blood 2011;118:3222-3227.

6. Anker SD, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009;361:2436-2448.

7. Verdon F, et al. Iron supplementation for unexplained fatigue in non-anaemic women: Double blind randomised placebo controlled trial. BMJ 2003;326:1124.

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9. Khorana AA, et al. Blood transfusions, thrombosis, and mortality in hospitalized patients with cancer. Arch Intern Med 2008;168:2377-2381.

10. Kim YT, et al. Effect of intravenously administered iron sucrose on the prevention of anemia in the cervical cancer patients treated with concurrent chemoradiotherapy. Gynecol Oncol 2007;105:199-204.

11. Steinmetz HT, et al. A new concept for the differential diagnosis and therapy of anaemia in cancer patients. Support Care Cancer 2010;19:261-269.