Safety concerns have arisen about the possibility of
erythropoiesis-stimulating agents (ESAs) promoting
tumor growth and increasing the incidence of venous thromboembolic events (
VTEs). Because of the reported presence of
erythropoietin receptors (EPORs) on
tumor cells, it was questioned if ESAs had the potential for promoting
tumor growth through stimulation of EPORs and
tumor vessels and/or enhanced
tumor oxygenation. Studies have shown that EPOR
mRNA can be isolated from
tumor cells, but the presence of EPOR
protein has not yet been proven because of a lack of specific
antibodies against EPORs. It is questionable whether EPORs on
tumor cells are functional and there is no evidence that ESAs (within the approved indication in patients receiving
chemotherapy) can stimulate EPORs on
tumor cells in vivo.
VTEs are frequent in
cancer patients, resulting from the effects of malignant disease,
cancer treatments, and comorbidities.
VTEs are a leading cause of death in
cancer patients. There are concerns about ESAs and a possible higher risk for
VTEs and shorter survival in
cancer patients. The higher risk for
VTEs associated with ESAs appears to be a class effect, but the risk may be particularly pronounced when ESAs are used off label, as seen in clinical trials that targeted
hemoglobin levels higher than those recommended by current ESA labeling and trials that enrolled patients who were not anemic at baseline. ESA treatment should be used within labeling confines.