Is Nephrology More at Ease Than Oncology with Erythropoiesis-Stimulating Agents? Treatment Guidelines and an Update on Benefits and Risks

Abstract

Erythropoiesis-stimulating agents (ESAs), which promote RBC production, have been extensively used to reduce transfusion requirements and improve quality of life (QoL) in both cancer patients and those with chronic kidney disease (CKD). However, the likelihood of response and duration of treatment differ in the two settings. In renal anemia, ESAs act straightforwardly as hormone-replacement therapy. The anemia of cancer, however, relates not to a lack of endogenous erythropoietin production but to diverse aspects of the disease (including a relevant inflammatory component) and chemotherapy. Response to ESAs is slower and less certain than in nephrology. In both settings, early studies showed that reversal of severe anemia was accompanied by substantial improvement in QoL. However, again in both settings, subsequent studies indicated that efforts to normalize hemoglobin might worsen outcome. In the context of cancer, this concern was reinforced by the suggestion that malignant cells had erythropoietin receptors and that its administration might therefore accelerate tumor growth, and moreover that cancer patients are more susceptible to venous thrombosis. The absence of these concerns for nephrologists, and their greater experience in managing ESAs and patients' iron status, may make them more at ease with ESAs than their counterparts in oncology. However, both groups of specialists have had to deal with reversals in recommended thresholds for intervention and restrictions imposed by regulatory authorities. In both specialties, the broad consensus now emerging is that the optimum balance of benefits and risks lies in using ESAs aimed at a hemoglobin level in the range of 11-12 g/dl, although for CKD patients there is still room for an individualized approach. The Oncologist 2009;14(suppl 1):57-62

Baseline characteristics of patients with chronic kidney disease stage 3 and stage 4 in spain: the MERENA observational cohort study

“…In our cohort, the mean hemoglobin was 10.3 g/dL during the initiation of ESA therapy. The use of ESA has been under great scrutiny and a moving target [24-27]. There is now a need to reevaluate the management of anemia in CKD and the data from this study will be timely.…”

Insights and Perspectives in the Clinical and Operational Management of Cancer-Related Anemia

“…ESAs were originally studied in chronic kidney disease, with the first publications examining their use in a nephrology setting appearing in 1986. 3,4 ESAs first came to market with the introduction of epoetin alfa in 1989, which was initially approved by the FDA for the treatment of anemia in patients with end-stage renal disease undergoing dialysis. The agent was marketed as Epogen by Amgen for the dialysis market and as Procrit by OrthoBiotech for other markets, including cancer and HIV/AIDS.…”

“…For patients with cancer-and chemotherapy-related anemia, data indicated that use of ESAs lowered dependence on transfusions, improved QoL, and reduced symptoms of fatigue. 3,6 In 2001, darbepoetin alfa, marketed by Amgen as Aranesp, came to market after a September approval by the FDA for the treatment of anemia associated with chronic renal failure. Darbepoetin alfa had already been approved in June 2001 by the European Medicines Agency (EMEA) for the chronic renal failure indication and the treatment of chemotherapy-induced anemia.…”