FDA Panel Supports Anemia Drugs for Cancer Patients

THURSDAY March 13, 2008 -- A U.S. Food and Drug Administration advisory panel voted Thursday to recommend continued use of blood-boosting drugs for cancer patients on chemotherapy, with the caveat that some cancer sufferers should steer clear of the medications.

The Oncologic Drugs Advisory Committee voted 13-1 for letting Amgen Inc. continue selling Epogen and Aranesp and Johnson & Johnson continue selling Procrit, according to the Wall Street Journal. But it also voted 11-2 to recommend against the drugs' use for cancer patients who are likely to be cured. And, in a 9-5 vote, the panel recommended the drugs not be used in patients with breast or head and neck cancer.

FDA briefing documents filed this week before the meeting showed there are eight clinical trials that now suggest these widely used medications actually speed the growth of tumors and shorten the lives of cancer victims. Known as erythropoiesis-stimulating agents (ESAs), they work by stimulating red blood cell production.

"Whereas at the time of approval safety concerns were theoretical, there is now mounting evidence of documented effects on survival, tumor progression, and thrombotic events which require a re-assessment of the net benefits of this class of drugs," FDA officials stated in the documents. "Based on data provided to FDA, there is no evidence that ESAs improve quality of life or cancer outcomes."

Reaction to the advisory recommendation was immediate.

"The panel based its decision on data that weren't statistically significant," said Dr. Samuel M. Silver, a spokesman for the American Society of Hematology. "The decisions were not based on hard science. There really wasn't any new information to change anything right now."

This issue is being driven by the fact that these are not primary therapy drugs, Silver said. "In addition, there is a feeling that they don't need the same level of evidence to look at adjunctive therapy as they do primary treatment drugs," he added.

"I wasn't surprised to see that they were trying to find a way to use it for patients who are getting chemotherapy for palliative care and not use it for patients for a curative intent, because of their concern of the tumor effects of the ESAs," Silver said.

Silver isn't sure, however, that the medications should be limited to palliative care. "Who makes the decision if it's curable or not? It's an interesting issue," Silver said. "I'm interested to see if this is going to pass muster in the FDA."

Silver also thinks that over the next four or five months, as the FDA considers the panel's recommendations, there will be changes. "They can't negate it all, but it will be interesting to see what comes out the other side," he said.

In statements released this week, both companies that sell the drugs defended their safety, when used according to recommended dosages, for the treatment of chemotherapy-induced anemia.

And following the panel's action, Amgen issued the following statement: "Amgen takes very seriously the safety signals seen in recent trials where ESAs were used outside of the labeled indication. ... We are committed to working with the FDA to consider the input from the committee and to implement future label changes," said spokesman David Polk.

Thursday's meeting is the latest in a long string of FDA actions concerning the potential dangers of these drugs since their approval in the early 1990s.

This isn't the only group of patients using ESAs that concerns the FDA. In kidney patients, past research has found that if these drugs are used to raise hemoglobin levels above 12 grams per deciliter of blood, the risk of death increases.

The growing body of evidence led the FDA to have the drugs' manufacturers add a "black box" warning to the medications last November. The warning indicates that the medications should be used at the lowest possible doses to avoid risks such as blood clots, heart attacks, stroke, congestive heart failure, increased tumor growth and an increased risk of death. The FDA also noted the trials generally indicated an increased risk when blood levels were raised above 12 grams per deciliter.

And last week, Amgen agreed to expand the "black box" warning on all three drugs to include information about tumor growth and death in patients with early-stage breast cancer and cervical cancer. Johnson & Johnson markets Procrit in an agreement with Amgen, the Wall Street Journal reported.

When Procrit was first approved in 1989, the drug was touted as a treatment to lessen fatigue and improve quality of life among cancer and HIV patients with anemia, but the revised label states there was no evidence to back that claim. The label change was the fifth such change since Procrit's approval, FDA officials said.

More information

For more on ESAs, go to the U.S. Food and Drug Administration.

Posted: March 2008


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