Erythropoietin-stimulating agents are only indicated for treatment of anemia in oncology patients with nonmyeloid malignancies when anemia is caused by palliative chemotherapy-induced myelosuppression. These agents should not be administered if treatment is of curative intent. ESAs should be discontinued following completion of a chemotherapy course.5,17-19 Guidelines and product labeling recommend ESAs should be used at the lowest dose possible to avoid transfusions, should be discontinued after 6 to 8 weeks in nonresponders, and should be avoided in patients with cancer who are not receiving concurrent chemotherapy except patients with low-risk myelodysplastic syndromes.6,11 ESAs may be used to treat patients with low-risk myelodysplastic syndromes when they are not currently receiving chemotherapy; this is the only oncology population to which this recommendation applies.

Hemoglobin levels should be monitored regularly in patients receiving ESAs. If a patient experiences a rapid increase in Hgb (an increase of more than 1 g/dL) or if the patient’s Hgb exceeds the level needed to avoid transfusion, the ESA should be held and subsequent doses reduced. ESAs should be discontinued in patients who discontinue chemotherapy as well as those who do not respond after 6 to 8 weeks.

Functional iron deficiency frequently occurs following continued ESA treatment. Rapid RBC production from ESAs increases the rate of iron mobilization from the reticuloendothelial system (RES) to the bone marrow. In addition, release of iron from the RES can be delayed by chemotherapy and the tumor itself. Functional iron deficiency leads to blunted ESA response.20 Therefore, iron stores (iron, ferritin, total iron-binding capacity, transferrin saturation) should be assessed prior to treatment with an ESA, periodically during treatment, and in patients who are not responding to treatment. Intravenous iron supplementation may be required.


The FDA instituted the Risk Evaluation and Mitigation Strategy (REMS) program in March 2008. The REMS program was initiated to ensure that the benefits of particular drugs continue to outweigh the risks. Drugs or biologic agents that pose significant toxicity or risk to patients are included in the REMS program, which has three components: (1) a medication guide, (2) a communication plan for health care providers, and (3) elements that assure safe use of the agent. The components that are required for a drug are dependent on the severity of the risks; not all drugs require all three components.21 ESAs were added to the REMS program in February 2010 and require all three components of the program.

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The manufacturers created the ESA Assisting Providers and cancer Patients with Risk Information for the Safe use of ESAs (APPRISE) Oncology program to aid health care providers in meeting REMS criteria. Health care providers must enroll in the program and complete training to satisfy the requirements for the REMS program. For each hospital that dispenses ESAs, a hospital designee must enroll in ESA APPRISE. This designee is responsible for establishing and overseeing the measures to promote safe and appropriate ESA use. Prescribers of ESAs must also complete the training and enrollment process. Health care providers and hospitals must re-enroll in the program every 3 years. Repercussions of failing to adhere to training, enrollment, or re-enrollment requirements of the program include suspension of access to the agents.

REMS criteria require providing patients with a medication guide and counseling on the risks versus benefits prior to initiating treatment. Counseling may be performed by nurses or other qualified health care providers.22 The patient medication guides, as well as enrollment documents and other helpful forms, are available through the ESA APPRISE Web site ( Although other information may be given to the patient if desired, the ESA APPRISE medication guide must be given to the patient. Patient counseling must be documented via the patient’s signature on the Patient Acknowledgement Form, provided through the program. A copy of the signed Acknowledgement form should be faxed or mailed to the ESA APPRISE program. If administered in a hospital, the signed form should be given to the hospital designee. A copy of the signed form may also be given to the patient.


Based on the data on their risks and benefits, ESAs should only be used to treat anemia in oncology patients who are receiving chemotherapy for palliation. Although ESAs reduce transfusion requirements, they have not been consistently shown to alleviate fatigue or symptoms associated with anemia. Multiple meta-analyses have shown that ESAs increase the risk of mortality, tumor progression, and VTEs in oncology patients when used to achieve a target hemoglobin level of 12 to 15 g/dL. The FDA mandates that these risks and benefits be discussed with the patient prior to initiating treatment. The manufacturers support the mandate and developed ESA APPRISE, the REMS program for erythropoietin-stimulating agents. With a thorough understanding of the therapeutic use of ESAs, nurses can play an integral role in counseling patients receiving these agents. ONA 

Sarah Wenger is a Post Graduate Year 2 Oncology Pharmacy Resident, Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado. Lisa Thompson is assistant professor, Department of Clinical Pharmacy, University of Colorado Denver Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado.

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1. Spivak JL. The anaemia of cancer: death by a thousand cuts. Nat Rev Cancer. 2005;5(7):543-555.

2. Ludwig H, Strasser K. Symptomatology of anemia. Semin Oncol. 2001; 28(2suppl8):7-14.

3. Holzner B, Kemmler G, Greil R, et al. The impact of hemoglobin levels on fatigue and quality of life in cancer patients. Ann Oncol. 2002;13(6):965-973.