Anemia and Iron Deficiency in Cancer Patients: Role of Iron Replacement Therapy

Abstract

Anemia in cancer patients is quite common, with remarkable negative impacts on quality of life and overall prognosis. The pathogenesis is complex and typically multifactorial, with iron deficiency (ID) often being a major and potentially treatable contributor. In turn, ID in cancer patients can be due to multiple concurring mechanisms, including bleeding (e.g., in gastrointestinal cancers or after surgery), malnutrition, medications, and hepcidin-driven iron sequestration into macrophages with subsequent iron-restricted erythropoiesis. Indeed, either absolute or functional iron deficiency (AID or FID) can occur. While for absolute ID there is a general consensus regarding the laboratory definition (that is ferritin levels <100 ng/mL ± transferrin saturation (TSAT) <20%), a shared definition of functional ID is still lacking. Current therapeutic options in cancer anemia include iron replacement, erythropoietic stimulating agents (ESAs), and blood transfusions. The latter should be kept to a minimum, because of concerns regarding risks, costs, and limited resources. Iron therapy has proved to be a valid approach to enhance efficacy of ESAs and to reduce transfusion need. Available guidelines focus mainly on patients with chemotherapy-associated anemia, and generally suggest intravenous (IV) iron when AID or FID is present. However, in the case of FID, the upper limit of ferritin in association with TSAT <20% at which iron should be prescribed is a matter of controversy, ranging up to 800 ng/mL. An increasingly recognized indication to IV iron in cancer patients is represented by preoperative anemia in elective oncologic surgery. In this setting, the primary goal of treatment is to decrease the need of blood transfusions in the perioperative period, rather than improving anemia-related symptoms as in chemotherapy-associated anemia. Protocols are mainly based on experiences of Patient Blood Management (PBM) in non-oncologic surgery, but no specific guidelines are available for oncologic surgery. Here we discuss some possible approaches to the management of ID in cancer patients in different clinical settings, based on current guidelines and recommendations, emphasizing the need for further research in the field.

Prevalence and Causes of Anemia in Hospitalized Patients: Impact on Diseases Outcome

“…Recently, it has been demonstrated that iron metabolism is altered not only in IDA (absolute deficiency) where iron stores are depleted, but also in CDA [13]. During chronic inflammation, hepcidin, a hepatic hormone, increases greatly under interleukins stimuli.…”

Efficacy of intravenous iron treatment for chemotherapy-induced anemia: A prospective Phase II pilot clinical trial in South Korea

“…Anemia is a common complication in patients with cancer, particularly in those receiving chemotherapy. It has markedly negative effects on the quality of life and overall prognosis [1,2]. Cancer-and chemotherapy-induced anemia (CIA) may substantially affect survival and treatment efficacy, delay or limit therapy, and contribute to both fatigue and a diminished healthrelated quality of life [3].…”

Systematic review of guidelines for the diagnosis and treatment of iron deficiency anemia using intravenous iron across multiple indications

“…12 Iron deficiency, with or without anemia, may have significant consequences in many conditions, including impact upon quality of life (QOL), [13][14][15] increased length of hospital stays, 16 and increased mortality 17,18 and morbidity. 19,20 In the most recent update to the Global Burden of Disease Study, IDA was ranked as the fourth highest cause of years lived with disability from a total of 328 diseases and conditions and the fifth most prevalent condition with 1.24 billion cases (95% uncertainty intervals 1.21-1.28 billion). 21 Iron supplementation is the most commonly prescribed treatment for anemia, although other options exist, including erythropoeitic stimulating agents (ESAs) and blood transfusions.…”

“…21 Iron supplementation is the most commonly prescribed treatment for anemia, although other options exist, including erythropoeitic stimulating agents (ESAs) and blood transfusions. 19 Iron supplementation can be either oral or parenteral. Ever since the introduction of low-molecular-weight intravenous (IV) iron formulations, many of the adverse events traditionally associated with parenteral iron administration have declined.…”