The National Cancer Institute, citing encouraging scientific studies, has asked the U.S. Food and Drug Administration to markedly expand trials of a new cancer therapy that turns some of a patient's white blood cells into tumor-killers.
The institute's proposal, submitted last week, would make the treatment, developed by institute researchers, potentially available on an experimental basis to as many as 15,000 patients with severe kidney cancer or melanoma, a skin cancer, the diseases for which it appears most effective, according to Dr. Bruce Chabner, director of the institute's division of cancer treatment.
An FDA spokesman said the agency is reviewing the institute's request but has yet to reach a decision.
The call for wider use of the extensively publicized "interleukin-2/killer cell" therapy results in part from two favorable reports published today in the New England Journal of Medicine.
'End of the Beginning'
The reports are accompanied by an editorial saying that researchers are "at the end of the beginning of the search for a successful immunotherapy for cancer."
"What we have here is hopefully the dawn of a new approach to treating cancer," said Dr. Steven Rosenberg, chief of surgery at the institute. He pioneered the therapy and is the principal author of one of the new studies. "What it's ultimately going to be able to offer patients with cancer is hard to predict. But when you have a whole new way of dealing with the disease, obviously it opens the possibility for development that could be very meaningful and important."
The optimistic comments were balanced by cautions that major problems, such as frequent treatment failures, severe toxicities and high costs, still must be overcome. "This is not a treatment ready for widespread application; we need to develop it," Rosenberg said.
"It is not an easy treatment (to take) yet," said Dr. John R. Durant of the Fox Chase Cancer Center in Philadelphia, the author of the New England Journal editorial. In an interview, Durant called for expanded trials and predicted that tests involving more than 10,000 patients would eventually be necessary to refine the therapy. He said, "I am not optimistic that you can do this work rapidly; people will learn things as they go along."
Treatment Costs $20,000
The novel treatment costs about $20,000 and usually requires at least two weeks of hospitalization, including specialized monitoring in an intensive care unit. It differs from traditional cancer therapies, which attack tumors with drugs, radiation or surgery. Instead, the interleukin-2/killer cell approach attempts to stimulate the patient's immune system and restore its normal ability to prevent the development of tumors.
The therapy uses the protein interleukin-2, a natural immune system booster, to transform in the laboratory a patient's own white blood cells into activated tumor-killing cells called "LAK" cells. Such cells are then reinfused into the patient's blood stream through a vein, along with massive doses of interleukin-2.
In related experimental approaches, some patients are treated with interleukin-2 alone, which is less complicated and expensive, or interleukin-2 in combination with conventional anti-cancer drugs. So far, about 1,300 cancer patients have been treated with interleukin-2 in more than 100 ongoing studies, according to Cetus Corp. of Emeryville, Calif., the leading manufacturer of the drug and the company that supplied it for the studies cited in the New England Journal.
In the larger of the two studies, Rosenberg's research group presents data on ongoing studies at the National Cancer Institute in Bethesda, Md., involving 157 patients. According to the researchers, otherwise untreatable tumors disappeared in six of 62 patients with either kidney cancer or melanoma who received the combination therapy. Tumors shrank by more than 50%, defined as a partial response, in 12 additional cases.
The therapy has also been tested against other cancers. Of 26 colon cancer patients, one had a complete remission and two had partial responses. Of two patients with non-Hodgkin's lymphoma, one had a complete remission and one had a partial response. Other patients showed little or no benefit.
In total, seven of nine patients whose tumors disappeared are still in remission an average of 10 months after therapy, according to the report.
Severe Side Effects
But the study also highlighted the severe side effects of the therapy. Many patients developed confusion, comas, respiratory distress, severe fluid retention, low blood pressure and other problems. The researchers said most of the toxic effects resolved "promptly" after the treatment was completed, but four patients treated died as a result of complications.