Ethics Questioned : Patients Pay to Be Part of Cancer Tests
When Dr. Eugene Nakfoor learned a year ago that he was terminally ill with lymph cancer, he embarked on a desperate search for alternatives to full-body radiation. That search led the Michigan physician to this suburban Nashville community, where he has become a willing guinea pig in the nation’s war on cancer.
Nakfoor, 63, is among about 75 well-to-do Americans who, since May, have been paying as much as $35,000 each to receive the latest experimental cancer therapies that might prolong their lives--notwithstanding the considerable risks that often come with untested treatments.
Many of Biotherapeutics Inc.’s patients, like Nakfoor, ended up here only after being rejected by similar--but free--programs sponsored by the National Cancer Institute either because they did not meet certain medical criteria or because the programs were full.
New Procedure
Biotherapeutics, started last May by a former leading government cancer researcher, represents a major--and controversial--departure from established procedures for testing new cancer drugs and therapies.
Traditionally, clinical trials to test experimental therapies are financed at least in part by the government, private groups like the American Cancer Society or the pharmaceutical industry, but not by the patient. The ethical rationale is that the safety and efficacy of such therapies are largely unknown and therefore volunteers should not be charged.
There are more than 1,000 clinical trials going on around the country at any given time. But most are not full. The few that are full--and even over-subscribed--typically involve a new class of experimental therapies called biological response modifiers that some researchers see as promising.
Therapies Offered
And it is those therapies--which attempt to enhance the body’s natural capacity to fight cancer--that Biotherapeutics is offering to clients like Nakfoor.
The man behind Biotherapeutics is Dr. Robert K. Oldham, a highly respected former government cancer researcher who is embarked on a campaign to shorten the time it takes to prove or disprove the efficacy of promising therapies.
Oldham’s unique program has left the cancer establishment questioning the ethics of charging people for participating in experiments that may not benefit them. But Oldham says his firm serves both the needs of research scientists and the terminally ill.
“I really believe the privatization of research is an important new concept and a way to add to our abilities to do cancer research in this country. You have more flexibility in the private sector,” he said in a recent interview here.
Among Oldham’s critics is Dr. Vincent DeVita, director of the National Cancer Institute, where Oldham set up the NCI’s highly touted biological response modifiers program in 1980.
“He is selling experimental therapy that has not yet been shown to be useful. . . . (It’s like) paying for a pig in a poke,” DeVita said.
Nakfoor said he also had entertained “a lot of second thoughts” about going to Oldham. “But after I understood what he is doing, I thanked God someone with his credentials has a program. I had no alternative.”
When Nakfoor, an emergency room physician at a Lansing, Mich., hospital was diagnosed, he tried to get into four or five NCI-sponsored clinical trials. But his particular type of lymphoma was not the type being sought by the researchers. In order to reach standardized results, they were looking only for patients with localized lymphoma or lymphoma at a different stage of growth than Nakfoor’s.
One of those researchers told Nakfoor about Oldham.
Oldham launched his company in May, 1985, a year after quitting his government job. He believes that no two cancers are exactly alike and therefore every cancer patient requires a therapy that is individualized.
Oldham charges $19,400 to transform a patient’s lymphocytes into LAKS, or lymphokine activated killer cells, one of the very latest experimental cancer therapies currently also on trial by the National Cancer Institute for a limited number of patients.
Or, for a fee of $35,000, appropriately selected patients may order a mixture of monoclonal antibodies, another newly developed research therapy, that are “custom tailored” for the patient’s own tumor.
Nakfoor said some of his colleagues looked askance at his becoming involved in what they consider to be commercialized clinical research.
“But I think they are acting unfairly if they think there are big profits being made at the expense of the patient,” Nakfoor said.
Oldham receives the highly publicized interleukin-2, a biological response modifier, to produce the LAKS cells. He receives it without cost from Cetus Corp., a Northern California firm that has been authorized by the U.S. Food and Drug Administration to provide it to qualified physicians conducting research trials.
According to Dr. Walter Glinsmann of the FDA, charging patients for clinical research violates no FDA regulation as long as unfounded claims are not made for the therapy. The agency, he said, considers Oldham’s program as the practice of medicine, and therefore within the jurisdiction of the American Medical Assn., not the FDA.
No one has accused Oldham of being a bad scientist. But some, in addition to DeVita, have expressed grave doubts about the ethics of what they call “fee-for-service research.”
In a recent article in the New England Journal of Medicine, Dr. Stuart E. Lind, a cancer specialist at Massachusetts General Hospital, declared: “Since miracles are rare and the first patient to receive a new treatment is unlikely to be cured, the burden of being the first to try a treatment should not be compounded by the need to pay for it.”
Lind also wondered whether departing from conventional clinical research might deprive patients of the protection they receive from hospital institutional review boards, which are intended to ensure the integrity of the research programs.
Negative Results
For instance, Lind suggested, a researcher who has a proprietary interest in a therapy’s success might be inclined to not report negative results.
Oldham sees these issues in a different light.
Why, he asks, must advanced cancer patients with a limited time to live be deprived of therapies that leading scientists believe hold promise, provided that the standard precautions are taken to inform the patients of the risks?
Oldham also has a ready answer for the criticism that his program is only for the rich. Such critics, he said, are confusing medical care with medical research.
“Our services in the laboratory are clearly research,” he maintains. “This cannot be equated with care.” But that does not mean, he said, that some patients may not benefit from the therapy despite its experimental nature.
In any case, Oldham said, the NCI’s clinical trials also are guilty of unequal access because the number of patients in them is limited and not every patient who meets the medical criteria gets in. This is especially true for interleukin-2 activated cell therapy, he said.
Oldham insisted that he will publish all results, negative as well as positive, as soon as they are known. He said patients’ rights are being protected by an institutional review board at Baptist Memorial Hospital in Memphis, a University of Tennessee-affiliated facility where all patients to date have received the experimental therapies.
Oldham admits that he cannot yet prove his claim that he can do the research cheaper than the government and come up with results quicker. He blames “academic thinking” for the “bugaboo” that charging properly informed patients for treatment-related research is somehow improper.
“You can be sure that an academic scientist who makes what he thinks is an important discovery stakes out certain rights to that intellectual property before he publishes it to feed his own ego, his own laboratory and his own status in the university with all the things that are the currency of academia,” he said.
“His reward may not be commercial. It may be that he becomes a professor instead of associate professor. It may be he gets 3,000 square feet of space instead of 1,000 feet, or two additional technicians. It’s not a black-and-white thing.”
Interleukin-2 and monoclonal antibodies, two of four or five experimental therapies that Oldham’s company offers, are unlike chemotherapy because, for one thing, they seek to enhance the body’s immune response whereas anti-cancer drugs, in killing cancerous cells, often suppress the immune system at the same time by killing healthy cells as well. The biological response modifiers also can have toxic effects, however.
Many scientists hope that the biologicals, as they are called, will someday join surgery, radiation and chemotherapy as traditional modes of cancer therapy.
Although the evidence to support this hope is still in short supply, the use of very large doses of interleukin-2 to activate a patient’s white blood cells, or lymphocytes, received a large boost from a report published in December by NCI’s Dr. Steven A. Rosenberg.
Rosenberg described how he used a special machine to remove the lymphocytes from the patient’s bloodstream, placed them in laboratory dishes where they were activated with a large amount of interleukin-2 and then reinfused the lymphocytes into the patient.
In a limited study of 25 patients who no longer were responding to any conventional therapy, Rosenberg said, the experimental treatment resulted in at least 50% reduction in tumor size in 11 patients with colorectal, kidney and lung cancers and melanoma. The therapy has since been shown to be especially effective against kidney cancer.
The excitement caused by these favorable responses led NCI to announce last month that a clinical trial would be launched immediately involving about 300 patients with melanoma, colorectal or kidney cancer at six medical centers around the country to more thoroughly evaluate the new treatment.
Although Oldham’s company is not a part of that clinical trial, his preparation of the experimental therapy essentially is the same as NCI’s, he said.
Oldham makes much of his attempt to customize a “cocktail” of monoclonal antibodies for each patient’s tumor.
But scientists like Dr. Carl Pinsky, a key researcher in NCI’s biological modifier program at Frederick, Md., said it is questionable whether customizing is possible and, if so, that it makes any difference.
“The issue has to do with whether it can be shown that in a cancer patient there is a substance on the cancer cell that is distinct from similar substances on normal cells, so that an attack by the antibody will result only in an attack on cancer cells,” Pinsky said.
Oldham’s method contrasts with that of most other researchers who use antibodies that are selected for their specificity for attacking a type of cancer--lymph or breast, for example--rather than a particular patient’s lymph or breast cancer.
Because of various technical problems involved in trying to select the right antibodies against specific tumor cell substances, Pinsky said, it is “scientifically unsound to say that we know how to select” the right ones.
While the scientific argument is still unsettled, there are several reasons why some patients are willing to pay for customized monoclonal antibodies rather than to receive them free elsewhere.
Besides the difficulty that some patients have in finding a clinical trial that needs patients with their kind of cancer, a researcher may not accept particular patients because their physical and mental health are not compatible with the conditions dictated by the institutional review board at the hospital where the study is being conducted.
In the case of LAKS and some of the other biologicals, a larger problem may be that the publicity they receive attracts more applicants than the number of openings. The LAKS clinical trial, for instance, has only 300 openings.
According to Oldham, many of his 75 patients had not been able to meet the criteria of the NCI-financed trials.
At Biotherapeutics, unlike in the NCI trials, there is no restriction on the type of tumor that the medical team will accept for experimental therapy, as long as the patient no longer responds to conventional therapy and is healthy enough to withstand the rigors of the research treatment, according to Biotherapeutics’ co-founder and medical director, Dr. William West. Besides colon and kidney cancer and melanoma, the team is also exploring therapeutic effects on breast cancer and mesothelioma, a cancer associated with asbestos exposure, according to West, who worked for Oldham at NCI.
Most patients have come from the southeastern part of the United States, but some live elsewhere, including California.
Because his program has been under way for less than a year, it is too early to evaluate the results, Oldham said.
About one-third of the patients are physicians, scientists or family members of the two groups. Private health insurance or programs like Medicare pay for the hospitalization costs but may not cover the research conducted by Biotherapeutics.
For every 100 people who call to inquire about Biotherapeutics’ program, according to Oldham, about 25 end up having the necessary medical and financial qualifications to make it worthwhile traveling to Franklin for more extensive evaluation. Eventually, the physician said, three or four end up receiving therapy.
Oldham left NCI in 1984, after four years during which he built the biological response modifiers program from nothing to a $20-million program with 150 employees. He said he left because he thought he could get results in a private setting faster than in government.
“It is possible through the private sector to get the capital, and if you do that you can find the scientists, create the interest and do the science just the same way as it would be in the universities. And you can do it a hell of a lot less expensively,” Oldham said.
Before going to the NCI, he built the oncology department at Vanderbilt University, where he is still a faculty member.
The physician said three recent advances in biotechnology now make it possible for even a relatively small company like Biotherapeutics to have the necessary technical resources to engage in biologicals research. The three advances are recombinant DNA technology, which enables researchers to make large amounts of natural compounds such as interleukin-2; the discovery of hybridomas, which make possible the manufacture of monoclonal antibodies; and equipment that allows researchers to isolate and purify biological compounds.
“You don’t need a huge lab to do many of these things,” he said.
Both Oldham and NCI officials admit that biologicals could meet the fate of many an agent before them that had been thought to be the magic bullet.
But they, like Nakfoor, are betting on a different outcome this time.
