• 1/4/2008
  • web-based article
  • Steven Reinberg
  • health.usnews.com

Two new studies offer further evidence of the health risks posed by the anemia drugs known as erythropoiesis-stimulating agents (ESAs), U.S. officials announced Thursday.

The studies showed that patients with breast or advanced cervical cancer who took the drugs as treatment for chemotherapy-induced anemia died sooner or had more rapid tumor growth than patients not on the drugs, U.S. Food and Drug Administration officials said in a prepared statement.

On Nov. 8, the FDA approved new “black box” warnings on labels of the three ESAs — Aranesp, Epogen and Procrit. The warnings detailed the dangers to patients with cancer and patients with chronic kidney failure. Those dangers include heart attack, stroke, heart failure and cancer tumor growth and shortened survival, the FDA said.

The drugs had been touted as a treatment to lessen fatigue and improve quality of life among cancer, HIV and other patients with anemia, but the revised label said there was no evidence to back that claim. The label change was the fifth such change since Procrit was approved in 1989, FDA officials said.

Results of the two studies released Thursday were not among the six studies that led to the Nov. 8 label revision. Taken together, 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 didn’t get this therapy, the FDA said.

The FDA said it plans to discuss the new findings and re-examine the risks and benefits of ESAs for patients with chemotherapy-induced anemia at a public advisory committee meeting in the next few months.

“This new information further underscores the safety concerns regarding the use of ESAs in patients with cancer, which FDA addressed in previous communications,” Dr. Janet Woodcock, the FDA’s deputy commissioner for scientific and medical programs, chief medical officer, and acting director of the Center for Drug Evaluation and Research, said in the statement.

“FDA is reviewing these data and may take additional action. In the meantime, FDA recommends that health care providers review the risks and benefits of ESAs outlined in the product label and discuss this information with their patients.”

According to the FDA statement:

– On Nov. 30, Amgen Inc., manufacturer of the three ESAs — Aranesp, Epogen, and Procrit — provided the FDA with information from the 733-patient PREPARE study of women who received chemotherapy before undergoing surgery for breast cancer. After three years, 14 percent of the patients who received Aranesp to treat their anemia had died, compared to 9.8 percent who did not get the drug. Tumor growth was also faster in patients receiving 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 either Procrit to maintain hemoglobin levels above 12 grams per deciliter of blood or blood transfusions as needed. After three years, 66 percent of the patients who did not take Procrit were alive and free of cancer growth, compared to 58 percent who had received the drug.

In announcing the label revision in November, Dr. John Jenkins, director of the FDA’s Office of New Drugs, said, “We are emphasizing that ESAs should be used at the lowest dose necessary to avoid blood transfusions, since that is the only identifiable benefit for ESAs. Doctors should have discussions with their patients about whether to use ESAs at all.”

The three drugs are synthetic versions of a protein made in the kidney that tells bone marrow to produce red blood cells. The drugs are manufactured by Amgen, of Thousand Oaks, Calif. Procrit is marketed and distributed by Ortho Biotech LP of Bridgewater, N.J., a subsidiary of Johnson & Johnson.

For cancer patients, November’s revised warnings emphasized that the drugs can cause tumor growth and reduce survival among patients with advanced breast, head and neck, lymphoid and non-small cell lung tumors. This is especially true when the dose is designed to produce a hemoglobin level of 12 grams per deciliter of blood or more.

For hemoglobin levels less than 12 grams per deciliter, the label says there’s no evidence to determine if the drugs cause any of these problems, the FDA said.

The revised label also made it clear that ESAs should be used in cancer patients only when their anemia is caused by chemotherapy and not from other causes. Also, ESAs should be stopped when the patient’s chemotherapy has ended, the FDA said.

The revised label also said there’s no evidence that ESAs improve symptoms of anemia, quality of life, fatigue, or patient well-being in cancer patients or patients with HIV taking the drug AZT.