New guideline from ASH and ASCO recommends caution regarding ESA use in cancer patients

WASHINGTON, 27 oct 2010– An updated joint guideline by the American Society of Hematology (ASH) and the American Society of Clinical Oncology (ASCO) advises physicians about the appropriate use of erythropoiesis-stimulating agents (ESAs), a class of drugs that stimulate the bone marrow to produce more red blood cells, to treat cancer patients with chemotherapy-induced anemia. While the guideline cautions that ESAs are associated with shorter survival and increased risk of thromboembolism — blood clots — and tumor progression, it also recognizes their major benefit of reducing the need for red blood cell transfusions, which can potentially cause serious infections and adverse reactions in the immune system.

"This updated guideline offers clinicians the latest synthesis of the medical evidence surrounding use of ESAs in patients with cancer, including appropriate cautions where evidence is lacking or where risks may outweigh the use of ESAs," said J. Douglas Rizzo, MD, MS, Co-Chair of the guideline panel and Professor of Medicine at the Medical College of Wisconsin.

Those risks may include thromboembolism or even death, according to new data cited in the guideline, which suggests that physicians avoid the use of ESAs in cancer patients who are not receiving chemotherapy, except for those with myelodysplastic syndrome (MDS). At the same time, the guideline confirms the effectiveness of ESAs in sparing patients the need for transfusions, which can substantially impact quality of life. By recommending that physicians discuss individual risks and benefits of ESAs and blood transfusion with patients prior to therapy, the guideline recognizes the critical role of shared decision-making between the patient and the physician.

In addition to outlining the clotting risks of ESAs, the guideline makes specific recommendations on usage and provides insights into disease progression and patient survival. The guideline also details new thresholds for initiation and modification of ESAs, which are consistent with current FDA labeling.

Originally published in 2002 and last updated in 2007, the guideline was derived from analysis of individual patient data, various medical literature, and systematic reviews of published clinical trials. In developing the update, panel members considered all relevant literature published between January 2007 and January 2010. Additional evidence was considered when it was considered pertinent to each section of the updated guideline.

"These guidelines touch on almost all aspects of the use of ESAs in patients with cancer and MDS, as well as secondary issues, such as the role of iron supplementation," said Samuel Silver, MD, a member of ASH's Committee on Practice and Professor of Internal Medicine at the University of Michigan. "These are issues that confront practicing hematologists and oncologists on a daily basis, and we hope that these evidence-based recommendations will influence practice standards and result in better care for patients."

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The guideline will be published ahead of print on the websites of Blood (bloodjournal.org), ASH's scientific journal, and ASCO's Journal of Clinical Oncology (jco.org) at 4:00 p.m. on October 25. The guideline will be published in print in Blood on November 18 and in the Journal of Clinical Oncology on November 20.

Risks of Anemia Drugs in Chemotherapy Patients Are Bolstered

By Peggy Peck
ROCKVILLE, Md., Jan. 3 -- More research has strengthened an association between erythropoiesis-stimulating agents (ESAs) and an increased risk of mortality when the drugs are used for chemotherapy-induced anemia, the FDA said today.
The new data came from two studies of women with breast cancer or advanced cervical cancer, research that had not been included when the FDA ordered a label change two months ago about excess mortality and/or rapid tumor growth with ESAs. This warning was on the basis of six other studies.
In today's statement, the FDA said that "all eight studies show more rapid tumor growth or shortened survival when patients with breast, non-small cell lung, head and neck, lymphoid, or cervical cancers received ESAs compared to patients who did not receive this treatment. In all of these recent studies, ESAs were administered in an attempt to achieve a hemoglobin level of 12 g/dL or greater, although many patients did not reach that level."
The FDA said that on Nov. 30, Amgen, manufacturer of the three ESAs -- Aranesp, Epogen, and Procrit -- provided the agency with information from the 733-patient PREPARE study of women who received chemotherapy before undergoing surgery for breast cancer. After three years, 14% of the patients given Aranesp to treat their anemia had died, compared with 9.8% who did not receive the drug. Tumor growth was also faster in patients given Aranesp.
On Dec. 4, Amgen informed the FDA of the results of a study by the National Cancer Institute's Gynecologic Oncology Group of patients receiving chemotherapy and radiation for advanced cervical cancer. The patients were given Procrit to maintain hemoglobin levels above 12 g/dL or transfusions as needed. After three years, 66% of the patients who did not take Procrit were alive and free of cancer growth compared with 58% given the drug.
Janet Woodcock, M.D., the FDA's chief medical officer and acting director of the Center for Drug Evaluation and Research, said the new information does not require immediate action, but does underscore "the safety concerns regarding use of ESAs in patients with cancer."
She said the FDA would discuss the new data at a planned advisory committee meeting on ESA safety "in the next few months."
Meanwhile, she said the FDA would continue to review available data and "may take additional action." She said physicians should "review the risks and benefits of ESAs outlined in the product label and discuss this information with their patients."
Amgen is based in Thousand Oaks, Calif. Procrit is marketed and distributed by Ortho Biotech LP of Bridgewater, N.J., a subsidiary of Johnson & Johnson.