Management of Cancer-Related Anemia in 2011

Eric H. Kraut, MD

Erythropoietin-stimulating agents (ESAs), once considered miracle drugs that enjoyed widespread use for cancer-related anemia, fell into disfavor in 2007, when evidence demonstrated that ESAs decreased survival and time to disease progression in patients with cancer-related anemia whether or not they were on chemotherapy and/or radiation. At that time, ESAs were dosed to a hemoglobin >12 g/dL.

“We thought we had a wonder drug, but we learned otherwise,” said Eric H. Kraut, MD, professor at the Ohio State University Comprehensive Cancer Center in Columbus. Kraut posed the following questions to attendees at the NCCN’s 6th Annual Hematologic Malignancies Congress about issues related to the management of cancer-related anemia and ESAs:

• Which treatment is better for cancer-related anemia: transfusion or ESAs?
• What are the real risks of ESAs when dosed to a lower hemoglobin level?
• Which patients should be treated with ESAs?
• What is the role of iron therapy?
• Do we need more data to guide use of ESAs?

Patients should be counseled about the risks versus benefits of ESA therapy, Kraut said. It is well established that ESAs decrease the need for transfusions in patients on chemotherapy. The benefits of transfusion include sustained improvement in hemoglobin level, possible improvement in quality of life, and avoidance of the risks associated with transfusions. Major risks of transfusions are transfusion reactions, including urticaria and skin rash (occurring in about 1 in 50—100 patients), acute lung injury, acute and chronic infection, and iron overload. HIV infection is no longer considered a common risk of transfusion, Kraut noted. It occurs in only about 1 in 2 million patients.

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There are gaps in our knowledge about ESAs ”

—Eric H. Kraut, MD

“There are gaps in our knowledge about ESAs,” Kraut continued. “There are no data on the risks of ESAs in patients treated to hemoglobin levels <12 ng/dL, and there are no randomized trials on currently approved doses.”

NCCN, FDA, American Society of Clinical Oncology/American Society of Hematology, and Centers for Medicare & Medicaid Services have published revised guidelines for use of ESAs in patients with cancer. These sets of guidelines generally agree that ESAs should not be used in nontreatmentrelated anemia in patients with solid tumors. They state that it is reasonable to consider use of ESAs in myelosuppressive chemotherapy-induced anemia in patients treated with a curative intent, taking into account the need for transfusion and the potential frequency of that need. Patients who develop anemia on myelosuppressive chemotherapy without a curative intent should be evaluated on an individual basis, according to the guidelines. The FDA guidelines state that ESAs should never be used to treat patients with breast, head and neck, and non—small cell lung cancer, because the data suggest that these agents interfere with response to cancer treatment.

“A major change is that the new goal of treatment [for ESAs] is to avoid transfusion, rather than to treat to a specific hemoglobin level,” Kraut said.

ESAs should not be initiated in patients with hemoglobin >10 mg/dL. Before initiating ESA therapy, patients should be evaluated for thromboembolic risk, including family history and assessment of hypercoagulability. If a provider decides to treat a cancer patient with an ESA, the FDA mandates documentation by providers; each patient must be advised about risks versus benefits and sign a form, and providers have to enroll in a program called ESA APPRISE and recertify every 3 years.

Another important change in management is driven by the recognition that patients with cancer can be iron-deficient despite having high levels of endogenous ferritin. Now, intravenous iron is advised prior to and during ESA treatment, Kraut said. “Iron levels should be measured at intervals during ESA treatment. Iron supplementation may make it possible to give less ESA,” he said.

“Each patient is different. Keep up to date with information from new studies, including safety data from studies of ESAs in patients with lower hemoglobin levels. Patients must be counseled on risks and benefits,” Kraut advised.