Experimental Drugs for Chemotherapy- and Cancer-Related Anemia

Abstract

Anemia in cancer patients is a relevant condition complicating the course of the neoplastic disease. Overall, we distinguish the anemia which arises under chemotherapy as pure adverse event of the toxic effects of the drugs used, and the anemia induced by the tumour-associated inflammation, oxidative stress, and systemic metabolic changes, which can be worsened by the concomitant anticancer treatments. This more properly cancer-related anemia depends on several overlapping mechanism, including impaired erythropoiesis and functional iron deficiency, which make its treatment more difficult. Standard therapies approved and recommended for cancer anemia, as erythropoiesis-stimulating agents and intravenous iron administration, are limited to the treatment of chemotherapy-induced anemia, preferably in patients with advanced disease, in view of the still unclear effect of erythropoiesis-stimulating agents on tumour progression and survival. Outside the use of chemotherapy, there are no recommendations for the treatment of cancer-related anemia. For a more complete approach, it is fundamentally a careful evaluation of the type of anemia and iron homeostasis, markers of inflammation and changes in energy metabolism. In this way, anemia management in cancer patient would permit a tailored approach that could give major benefits. Experimental drugs targeting hepcidin and activin II receptor pathways are raising great expectations, and future clinical trials will confirm their role as remedies for cancer-related anemia. Recent evidence on the effect of integrated managements, including nutritional support, antioxidants and anti-inflammatory substances, for the treatment of cancer anemia are emerging. In this review article, we show standard, innovative, and experimental treatment used as remedy for anemia in cancer patients.

Keywords: cancer-related anemia; chemotherapy-induced anemia; energy metabolism; erythropoietin, interleukin-6; hemoglobin; inflammation; iron homeostasis.

Figure 1

Pathogenetic mechanisms of cancer-related anemia and main related targeted approaches. The pathogenesis of cancer-related anemia involves multiple mechanisms induced by chronic inflammation associated to cancer and leading to functional iron deficiency and impaired erythropoiesis. Then, a multitargeted approach including conventional treatment such as ESAs, blood transfusion, iron therapy, as well as drugs targeting the inflammatory pathway, modulators of the iron metabolism, hepcidin antagonists, novel regulators of erythropoiesis and nutritional support should be considered. Figure was created in BioRender.com.

Figure 2

Pathogenesis of chemotherapy-induced anemia and therapeutic strategies. Chemotherapy-induced anemia is related to the toxic effect of anticancer treatments on bone marrow or to a nephrotoxic effect, which negatively influence EPO production. Additionally, anticancer treatments can induce gastro-enteric side effects, such as anorexia, nausea, and vomiting, and diarrhoea, which lead to iron and vitamins deficiency. Thus, treatment includes ESAs, iron therapy (oral or intravenous iron) and nutritional support. Figure was created in BioRender.com.