Wider Use of New ‘Killer-Cell’ Cancer Therapy Sought
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.
Continuing Studies
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.
Interleukin-2/killer cell therapy first came to public attention in December, 1985, when Rosenberg, a highly respected researcher who also performed colon cancer surgery on President Reagan in 1985, published his initial results in 25 patients in the New England Journal. The Cancer Institute immediately received thousands of calls from patients who wanted to be treated.
Subsequently, Rosenberg was criticized by some researchers for portraying the therapy as a “breakthrough” against cancer, a charge that he has consistently denied.
Change of Position
Nevertheless, Rosenberg’s latest results have caused one of his leading public critics to back away from his earlier opposition to continuing the studies.
“I do not challenge (Rosenberg’s) current article scientifically or philosophically,” said Dr. Charles G. Moertel, a tumor specialist at the Mayo Clinic in Rochester, Minn. “I am very high on continued research.”
Last December, Moertel, in a scathing editorial in the Journal of the American Medical Assn., called upon the Cancer Institute to stop testing the immune system treatment, saying that it had no role in “the compassionate management of patients with cancer.”
Currently, the therapy is available only at the institute and at six medical centers, including the City of Hope in Duarte and the University of California, San Francisco, and some private clinics where patients pay for experimental treatments.
Federally Sponsored Centers
If the institute’s proposal to expand the cancer immunotherapy trials is approved, the agency will offer the therapy to 38 federally sponsored cancer treatment centers, which would decide individually whether to participate in the expanded trials, the institute’s Chabner said.
In California, these additional centers would include UCLA, USC, University of California, San Diego, and Stanford, through the Northern California Cancer Center in Belmont.
Chabner acknowledged that some centers might decide against offering the therapy, in part because the institute has no plans to distribute additional funds specifically earmarked to cover the costs of treating additional patients. By comparison, the institute pays all treatment costs in the ongoing federally sponsored trials. The interleukin-2 has been supplied without charge by Cetus, but a spokesman said if the trials are expanded the company might seek to recover some of its costs from the Cancer Institute.
Study at Private Clinic
The second New England Journal study, involving cancer treatments with high doses of interleukin-2 alone, was conducted at the Biological Therapy Institute and Biotherapeutics Inc. in Memphis and Franklin, Tenn., a for-profit private clinic where patients pay to receive experimental therapies. The study was designed to determine a safer way to administer the treatment.
Of 40 patients who could be evaluated, 13 had partial reponses to the therapy, including five with melanoma and three with kidney cancer. There was one treatment-related death.
Since February, 1986, the Cancer Institute also has been conducting national trials of interleukin-2/killer cell therapy to try to confirm Rosenberg’s results. These tests involve about 100 patients at the City of Hope, UC San Francisco and four other medical centers.
The preliminary results of the nationwide trials, which will will be presented at the American Society of Clinical Oncology meeting in Atlanta in May, “essentially show the same response rate in melanoma, a somewhat lower response rate, but definite activity, in kidney cancer, and the same levels of toxicities,” Chabner said.
