In 2007, the Centers for Medicare and Medicaid Services (CMS) issued a National Coverage Determination (NCD) for ESAs, which limits their use among patients with anemia resulting from concomitant therapy.6 In August 2008, a new product label was issued that included restricting the initiation of ESAs to hemoglobin levels below 10 g/dL, restricting maintenance admissions to the lowest dose required to avoid transfusions, and identifying ESAs as not indicated for chemotherapy treatment that has curative intent.6 In 2010, the ESA Assisting Providers and Cancer Patients with Risk Information for the Safe Use of ESAs (APPRISE) Oncology program began.7

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The American Society of Clinical Oncology (ASCO) and the American Society of Hematology (ASH) have repeatedly issued joint clinical practice guidelines about the use of ESAs in adults with anemia induced by chemotherapy.8 Clinicians are counseled to discuss potential harms and benefits from ESAs and from red blood cell transfusions with patients experiencing chemotherapy-induced anemia with a hemoglobin level below 10 g/dL. Like the CMS guidelines, the ASCO-ASH guidelines caution against using ESAs under circumstances other than chemotherapy-induced anemia. If the decision to use ESAs is made, the lowest possible dose should be used; hemoglobin levels should be increased to the lowest possible concentration to help avoid the need for transfusions. As recommended in the product labeling and in practice guidelines, the use of ESAs should be minimized in patients whose malignancies are being treated with curative intent.8

In 2009, a meta-analysis of 13,922 patients examined the effects of ESAs on the survival of patients with cancer.5 Mortality was increased by 17% in those receiving ESAs relative to control patients, and by 10% in those undergoing chemotherapy. The author noted that thromboembolic and cardiovascular events may be caused by ESAs, independent of hemoglobin concentrations.5

Notably, among patients who are properly treated with ESAs, the use of ESAs does not decrease overall survival or cause tumor progression to occur.2 Negative results on survival occurs for those patients who continue to receive ESAs despite a lack of response, particularly for those who both fail to respond to treatment and also receive a blood transfusion. The safety concern for venous thromboembolism remains consistent due to its increased overall risk of 1.6. Certainly, when considering the safety of ESAs, those concerns must be balanced against the safety of a blood transfusion.2

Effects of Changes in Erythropoiesis-Stimulating Agent Use

A recent retrospective longitudinal study examined how hemoglobin levels changed in community oncology clinics before and after the NCD and new ESA product label were issued.6 Records were examined from January 2006 through July 2009 for 4,654 episodes of chemotherapy. A total of 23.7% of the cancer patients had baseline hemoglobin <11 g/dL. Among 4,864 episodes of anemia for the 4,021 patients, 40.2% were treated for anemia.6 Episodes without anemia treatment increased from 44.6% in 2006 to 77.81% in 2009 (P<0.05).6

The use of ESAs decreased from 45.5% in 2006 to 11.5% in 2009; conversely, transfusion rates increased from 3.4% in 2006 to 8.73% in 2009 (P<0.05 for both).6 From 2006 to 2009, the average hemoglobin level was lower by 1 g/dL to 1.9. Results also showed that initiation of treatment occurred later in the episode and at a lower starting hemoglobin level in the patients who were treated for anemia.6