Erythropoiesis-stimulating agents (ESAs) are medications that help treat anemia caused by chemotherapy. Anemia is an abnormally low level of red blood cells (RBCs). RBCs contain hemoglobin (an iron protein) that carries oxygen to all parts of the body. Chemotherapy can cause anemia because it can make it harder for the body to produce new RBCs. If the level of hemoglobin is too low, parts of the body do not get enough oxygen and cannot work properly. The use of ESAs, such as epoetin (Epogen, Procrit) and darbepoetin (Aranesp), is the subject of a clinical practice guideline from the American Society of Clinical Oncology (ASCO) and the American Society of Hematology (ASH). Cancer.Net talked with Alan Lichtin, MD, to learn more about these drugs and what people with cancer should know about them.

Q: How was the ASCO-ASH clinical practice guideline for the use of ESAs developed?

A: The guideline was developed by a panel composed of doctors who specialize in cancer, specialists on quality of life, and a cancer survivor. The panel reviewed all of the studies published since the original guideline was published in 2002. These studies are known as randomized controlled clinical trials, which are research studies that assign people to different groups randomly (like the flip of a coin). Most of the studies randomized patients to either receive an ESA to treat or prevent anemia, or to receive blood transfusions if they became necessary.

Q: Why may doctors prescribe ESAs for people with cancer?

A: If your doctor feels that you are or will be at risk for needing a blood transfusion because of your chemotherapy, he or she may discuss the option of ESA treatment with you. ESAs are approved to decrease blood transfusions. They have not been shown to improve survival or quality of life in patients receiving them. Because ESAs can take from two to six weeks to take effect, they are usually started before you reach a hemoglobin level at which you would need a transfusion. Both blood transfusions and ESAs have risks and benefits, so talk with your doctor about which one may be right for you.

Q: What types of chemotherapy are more likely than others to cause anemia?

A: In particular, platinum-containing chemotherapy, such as cisplatin (Platinol) and carboplatin (Paraplatin), are more likely to cause anemia, though other chemotherapy may cause anemia.

Q: What are the situations in which ESAs are not appropriate for use by people with cancer?

A: ESAs are not appropriate for people with cancer who are not receiving chemotherapy, and people with blood cancers other than myeloma, non-Hodgkin lymphoma, and chronic lymphocytic leukemia (CLL). People with acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML) should not take ESAs.

Q: What questions should patients ask their doctors about chemotherapy-related anemia and ESAs?

A: Patients should ask their doctors what is the cause of the anemia, what is the best way to treat it, how will the treatment help, and what are the possible risks of the treatment. A complete listing of helpful questions to ask your doctor is available in the What to Know: ASCO's Guideline on Epoetin and Darbepoetin Treatment.

A: This is an area of controversy. Published studies show that the use of ESAs may, indeed, cause an increased risk of blood clots, heart attacks, and strokes. This seems to be more likely when the hemoglobin level rises rapidly, or when the hemoglobin gets above the 10-12 grams per deciliter (g/dL) hemoglobin range. Also, recent data suggest that patients' tumors might grow more rapidly when ESAs are given. This seems to come mostly from studies where patients received ESAs in the absence of chemotherapy. In the guideline, ASCO and ASH advocate for a future research agenda to address these concerns. Patients should discuss the various options for treating and preventing anemia with their doctors. Ultimately, it's up to the physician and the patient to weigh the risks and benefits of ESAs, and make a rational judgment for recommending and accepting them, respectively. It's also up to the patient to share in the process of making this decision.

Q: What additional research is needed to learn how to better use ESAs for people with cancer?

A: More information is needed on what increases the risk of side effects from ESAs and the risk of needing RBC transfusions. How ESAs may affect some patients' survival, and how changes in hemoglobin level may affect quality of life are other areas that need more research.

Dr. Lichtin is a staff physician in the hematologic oncology and blood disorders department at Cleveland Clinic. He is Co-Chair of the ASCO/ASH Epoetin and Darbepoetin Update Expert Panel and a member of the ASCO Health Services Committee.

More Information

What to Know: ASCO's Guideline on Preventing and Treating Blood Clots

Managing Side Effects: Anemia