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Iron Deficiency Anemia in Cancer Patients

Mark Janis
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Published Online: Jun 25th 2012 Oncology & Hematology Review (US), 2012;8(2):74-80 DOI: https://doi.org/10.17925/OHR.2012.08.2.74
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1

Abstract

Overview

Anemia is highly prevalent, affecting approximately 40 % of cancer patients, and results in a significant decrease in health-related quality of life while also being associated with shorter cancer survival times. A recent survey of 15,000 cancer patients in Europe found that 39 % were anemic at the time of enrolment. In addition, anemia is a recognized complication of myelosuppressive chemotherapy, and it has been estimated that, in the US, around 1.3 million cancer patients who are not anemic at the time of diagnosis will develop anemia during the course of their disease. The etiology of anemia in cancer patients is variable and often multifactorial, and may be the result of an absolute or a functional iron deficiency. Cancer produces an enhanced inflammatory state within the body—causing hepcidin levels to increase and erythropoietin production to decrease—and results in a reduction in erythropoiesis due to impaired iron transport. This type of anemia is known as functional iron deficiency, where the body has adequate iron stores but there are problems with mobilization and transport of the iron. Absolute iron deficiency is when both iron stores and iron transport are low. The National Comprehensive Cancer Network (NCCN) treatment guidelines for cancer-related anemia recommend intravenous (IV) iron products alone for iron repletion in cancer patients with absolute iron deficiency, and erythropoiesis-stimulating agents (ESAs) in combination with IV iron in cancer patients (currently undergoing palliative chemotherapy) with functional iron deficiency. Although IV iron has been demonstrated to enhance the hematopoietic response to ESA therapy, the use of supplemental iron has not yet been optimized in oncology. Here we discuss the significance of iron deficiency anemia in cancer patients and the need to implement tools to properly diagnose this condition, and we provide an overview of the management strategies and recommendations for patients with iron deficiency anemia as outlined in the NCCN guidelines.

Keywords

Anemia, functional iron deficiency, absolute iron deficiency, iron deficiency anemia, hepcidin, erythropoiesis, erythropoiesis-stimulating agents (ESAs), cancer-related anemia, National Comprehensive Cancer Network (NCCN) guidelines

2

Article

Anemia is defined by the World Health Organization as a hemoglobin (Hb) level <13 g/dl for men and <12 g/dl for women,1 and can be further subcategorized into mild (>10 g/dl), moderate (8–10 g/dl), severe (6.5–8 g/dl), and life-threatening (<6.5 g/dl) ranges. Anemia is a common comorbidity in cancer patients. It is multifactorial, with causes including nutritional deficiencies of iron, folate, or vitamin B12; renal disease; bone marrow involvement; blood loss; effects of cancer therapies; inflammation or activation of the immune system; and autoimmune hemolysis. Signs and symptoms of anemia include weakness, fatigue, pallor, tachycardia, dizziness, shortness of breath, and cognitive impairment. Anemia is highly prevalent in cancer patients; in fact, the analysis of data from over 15,000 patients enrolled in the European cancer anemia survey (ECAS) showed that 39 % were anemic at the time of enrolment in the survey2,3 and, in patients undergoing certain anticancer therapies or with particular types of cancer, this number can be as high as 90 %.4 Other factors that affect the frequency of anemia in cancer include advanced age and comorbidities such as renal dysfunction.5 It has been estimated that, of the approximately 10 million individuals in the US who have cancer, about 1.3 million who are not anemic at the time of diagnosis will develop anemia at some point during the course of their disease.6

In the previously mentioned ECAS study, cancer-related anemia was most frequently reported in patients with gynecological cancer (81.4 %), lung cancer (77 %), and lymphoma/myeloma (72.9 %).2 In addition, this study indicated that the longer patients received chemotherapy, the higher their risk of becoming anemic. Anemia is also a recognized complication of myelosuppressive chemotherapy in cancer patients.

Platinum-based chemotherapy regimens—such as those commonly used in lung, ovarian, and head and neck cancers—have combined kidney and bone marrow toxicity, and are well known as inducers of anemia.7 The myelosuppressive effects of chemotherapeutic regimens accumulate during therapy, meaning that the rate of anemia in cancer patients increases with additional treatment cycles.8 This cumulative effect has been documented in the ECAS survey, where the prevalence of anemia was shown to increase from 19.5 % in the first cycle of chemotherapy to 46.7 % after the fifth cycle.2 Significant predictive factors for the risk of developing anemia following chemotherapy include having a lower initial Hb level prior to treatment; having lung or gynecologic cancer versus gastrointestinal (GI)/colorectal cancer; having cancer at any other site versus GI/colorectal cancer; and treatment with platinum-based chemotherapies.9

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3

Article Information

Disclosure

Mark Janis, MD, is on the board of speakers for AMAG and Pathworks Diagnostics.

Correspondence

Mark Janis, MD, Suite 207, 3801 Katella Avenue, Los Alamitos, CA 90720, US. E: dinkylee@aol.com

Support

The publication of this article was funded by AMAG Pharmaceuticals. The views and opinions expressed are those of the author and not necessarily those of AMAG Pharmaceuticals.

Received

2012-08-24T00:00:00

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