Erythropoietic Therapy for Cancer-related Anemia

US Oncology Review, 2005;1(1):1-6

Abstract:

Introduction
Anemia is the most common hematologic abnormality seen in malignant conditions, occurring in more than 50% of patients.1 This carries a prevalence in the US approaching 900,0002 and leads to debilitating symptoms, impaired health-related quality of life (HRQOL), and possible causative roles in reduced survival outcomes and cognitive impairment with chemotherapy.Approximately three-quarters of anemic cancer patients are considered as having chemotherapyinduced anemia (CIA) with the remainder designated as the chronic anemia of cancer (AoC).3

In the setting of cancer, anemia is prevalent due to many possible etiologic factors including blood loss, nutritional deficiency, hemolysis, hypersplenism, hemophagocytosis, and impairment of bone marrow function through such mechanisms as myelosuppression, tumor involvement, hypoplasia, myelofibrosis, and myelodysplasia. However, even in the absence of these complicating factors, anemia remains prevalent and, as such, comprises one subset of the anemia of chronic disease.4

Citation US Oncology Review, 2005;1(1):1-6

Inflammatory cytokines, especially interleukin (IL-1), interferon-gamma (IFN- ?), and tumour necrosis factor (TNF), reduce erythropoietin (EPO) production, suppress the bone marrow’s response to EPO, and alter ferrokinetics.5 The majority of anemic cancer patients will not represent a ‘pure’ anemia of cancer as approximately 75% will have had chemotherapy and/or irradiation at some point historically,6 with the associated myelosuppresssion from these modalities.In the setting of cancer, anemia is prevalent due to many possible etiologic factors including blood loss, nutritional deficiency, hemolysis, hypersplenism, hemophagocytosis, and impairment of bone marrow function through such mechanisms as myelosuppression, tumor involvement, hypoplasia, myelofibrosis, and myelodysplasia. However, even in the absence of these complicating factors, anemia remains prevalent and, as such, comprises one subset of the anemia of chronic disease.4 Inflammatory cytokines, especially interleukin (IL-1), interferon-gamma (IFN- ?), and tumour necrosis factor (TNF), reduce erythropoietin (EPO) production, suppress the bone marrow’s response to EPO, and alter ferrokinetics.5 The majority of anemic cancer patients will not represent a ‘pure’ anemia of cancer as approximately 75% will have had chemotherapy and/or irradiation at some point historically,6 with the associated myelosuppresssion from these modalities.

Erythropoietin
While it had been recognized for almost a century that a circulating substance regulated mammalian erythropoiesis, the glycoprotein EPO was not isolated until Miyake7 did so in 1977 from the urine of subjects with aplastic anemia, owing to EPO’s normal presence in such minute quantities. By 1985, EPO DNA probes were employed to isolate and then clone the gene.8,9 Then, with incredible rapidity, recombinant human (rh)EPO was produced by recombinant DNA technology, employed in clinical trials, and gained regulatory approval in 1989 as epoetin alfa for the treatment of anemia in dialysis-dependent end-stage renal disease.