Cancer researchers are embroiled in a dispute with the Food and Drug Administration over the safety of an experimental radio-wave machine that is designed to heat malignant tumors to the point that they can no longer grow inside the human body.
The technique on which the device is based is known as hyperthermia and has long promised to become the fifth mode of cancer therapy, along with surgery, radiation, chemotherapy and immunotherapy.
While it has not proved to be a cure, hyperthermia over the last decade has proven effective, especially in combination with drugs and radiation, in shrinking cancerous growths to the point that they can be surgically removed. Even in cases where further treatment is not feasible, patients have been relieved of pain and have had their lives extended by the relatively painless procedure, according to reports that have appeared in prestigious oncology journals in recent years.
Last month, however, the FDA sent a letter to Dr. F. Kristian Storm III, former professor of surgery at UCLA and now chairman of surgical oncology at the University of Wisconsin, Madison, saying that the agency was immediately withdrawing its approval of a hyperthermia device that Storm helped design and has been testing with the assistance of 12 researchers at nine institutions, including UCLA, over the last decade.
As a result, all prototypes of the device have been shut down and patients have been taken off treatment.
Although the FDA said in its letter that there is a possibility of appeal, the case represents the end of a running battle between the FDA and the nine institutions over the effectiveness of the procedure and the desirability of using painful--and what some believe are dangerous--probes to monitor the progress of terminally ill cancer patients who are undergoing hyperthermia treatment. Moreover, the case illustrates the uncertainties and long delays that researchers say they constantly face in dealing with the FDA.
Lack of Proof Cited
In a letter dated Oct. 6, Robert Sheridan, acting director of FDA’s Office of Device Evaluation, said that the researchers who have used the so-called magnetrode hyperthermia system concentric coil applicator have failed to prove either its effectiveness in treating tumors deep within the body or its safety both for patients and technicians.
Specifically, the FDA letter said, the agency was turning off the machines because of the researchers’ repeated failure to monitor the internal temperatures of patients during treatments.
Moreover, the agency said, the radio-wave machines have the potential to leak radiation of “potentially significant levels” and harm medical personnel standing nearby and to cause other problems, such as sterility, in patients who are being treated.
In interviews over the last two weeks, researchers who have used the radio-wave device said they have told the FDA that they are willing to monitor the temperature of tumors and internal organs during initial treatments but are unwilling to do so on a repeated basis during follow-up treatments because the probes are large, painful to insert and potentially hazardous to cancer victims, whose bodies are highly subject to infection.
The manufacturer of the system also acknowledged that there is potential for radiation leaks in the system but insisted that such leaks are well within established safety limits and that all technicians operating the devices were well-informed of the hazards, just as are dental assistants who take certain precautions when taking X-rays.
The FDA letter ordering the shutdown did not say why, after nearly a decade of testing, the drug agency had decided that there was enough “unreasonable risk to the public health” that the machines should cease operations abruptly. Last week, FDA officials refused any comment on the matter, saying that questions concerning these and any other experimental medical devices are a matter of “proprietary interest” and are therefore strictly confidential.
Although few in the cancer research community had heard of the FDA’s action or understood the reasons behind it, numerous researchers and physicians contacted by The Times endorsed hyperthermia as an important weapon in the battle against cancer and praised the physicians who have been involved in this particular hyperthermia project.
The FDA’s decision set off an angry response from those who have been involved in testing the device. Among the group of 12 physicians and scientists are some of the most prominent names in cancer today, including past presidents of the American Cancer Society and the prestigious Society of Surgical Oncology.
“These people involved in the project are not charlatans,” said Storm, who was a full professor of oncology at UCLA when he left Los Angeles last year to start a new surgical oncology unit at the University of Wisconsin. “There is no scientific basis whatever for what the FDA has done. . . . I don’t know how these people (at the FDA) sleep at night. . . . It’s been a total frustration. We thought we would have this thing approved and on the market five years ago.”
Ted Henry, president of Henry Radio and Henry Medical Electronics Inc., a family operated company in Los Angeles that manufactures the machine, said: “The FDA’s demands are unreasonable as far as I’m concerned. . . . They have taken a safe, relatively painless non-invasive procedure and turned it into a daily surgical treatment . . . which is what the insertion of the temperature probes amounts to.”
“It’s absolutely absurd,” said Dr. Donald L. Morton, chief of surgical oncology at UCLA, who has been involved with the project for years and published research articles on the subject.
“To say (that patients) may become sterile (from stray radiation associated with this treatment) is absurd,” Morton said. “Understand who these patients are. They are ones who have already undergone chemotherapy and radiation treatments, and they have failed. I’d be delighted if they were around long enough to become sterile.”
Storm said he believes that the FDA has “no conception of what the device is. I’ve sent them a foot and a half of data--literally. And it’s clear they haven’t read any of it.”
“I can’t honestly explain why they have done this,” he said. “The FDA answers to no one.
“I’ve been told that FDA isn’t ready for a deep-heating device. And I guess that’s what they’ve told us: They’re not ready, no matter what the data show.”
According to published reports in a number of scientific journals, ranging from Cancer to the American Journal of Surgery, the radio-wave machine has been used in about 18,000 treatments on 1,500 patients in nine research hospitals from Oregon to Alabama. Besides UCLA, machines have been operated in two other California hospitals: Desert Hospital, a USC affiliate in Palm Springs, and Pomona Valley Community Hospital, a Loma Linda University affiliate in Pomona.
In one-third of the cases reported, the tumors stopped growing and the patients stabilized. In another third of the cases, the tumors began to shrink and patients, many of whom were bedridden and taking narcotics to kill their pain, began to improve and reported feeling better.
“It’s not a cure,” Storm said. “What it does is give a few more months, if not years, of quality existence. I know it has helped patients where nothing else has.”
The use of heat to kill cancer is not a new idea. Western physicians have been interested in the notion since Hippocrates reportedly achieved a modicum of success by placing hot pokers into tumors. Even further back, a 5,000-year-old Egyptian papyrus seems to refer to a type of hyperthermia treatment when it talks of a fire “drill,” or heated stick, used to pierce tumors. More recently, 19th-Century physicians observed that malignant growths sometimes disappeared when patients developed high fevers.
Studies in the ‘60s
But use of hyperthermia in modern medicine did not come into full play until the 1960s. By that time, scientists understood some of the fundamental physiology and biochemistry of tumors.
Most cancers, scientists found, have poor circulation in comparison to normal tissue. Normal tissue is able to dissipate heat by dilating blood vessels, thereby allowing more blood to pass through and carry heat away. But tumors seem to have blood vessels that do not have such capacity and are thus “compromised” or destroyed by exposure to unusually high temperatures.
Over the years, a variety of methods of heating tumors have been tried: pumps to warm the blood, devices to focus ultrasound waves, machines that direct electromagnetic waves--microwaves and radio waves--into the tumor.
For nearly a decade, for example, Dr. Michael Salcman, a neurosurgeon at the University of Maryland Medical School, has been testing and redesigning a microwave system that he hopes will substantially extend the lives of patients with brain tumors within the next few years. Under conventional treatment, only about 10% of the patients he is treating could hope to have a survival rate of even two years.
Focusing the Heat
Unlike Storm’s device, Salcman’s system involves an operation in which antennae and probes are implanted inside the brain so that both microwave heat and radiation can be directed precisely at the diseased tissue. Some patients are also given doses of chemotherapy in combination with hyperthermia. Salcman says that the point of his treatment is not to heat the cancer cells to the point where they are destroyed, but to raise the temperature of the tumor to a degree that it is more susceptible to more conventional forms of treatment.
Most researchers agree that the process of hyperthermia, however it is administered, seems to work best when done in conjunction with chemotherapy or standard radiation. In many cases, it seems, the deep heat renders cancer cells more vulnerable to treatments at dosages that are not as toxic to the rest of the body.
Salcman said he, for one, has not had any difficulties with the FDA over the use of his hyperthermia technique. He conducted a trial in 1980 and has just begun two more hyperthermia trials.
Like the FDA, however, he said, he had some misgivings about any experimental technique that would not allow physicians to monitor at all times precisely the amount of heat that was reaching internal organs.
“Maybe I am unduly sensitive to this issue simply because I am dealing with the brain and not some other less-sensitive organ of the body,” Salcman said.
But researchers involved in testing Storm’s competing radio-wave unit said their device differs in design from other machines and is, they believe, fundamentally superior.
Because the magnetrode system uses radio waves and radio waves vibrate at a lower frequency than microwaves, they have a less deleterious effect on normal tissue and do not need to be as carefully controlled. Despite their greater safety for normal tissue, radio waves seem to cause enough damage to tumors to make them stop growing, and in some cases begin to shrink.
With tumors on or near the surface of the body, the type of heat source makes little difference, Storm said. But the use of a potentially destructive form of heat, such as microwaves, on tumors in organs deep within the body can cause such serious problems that physicians are forced to repeatedly insert temperature probes to avoid burning skin, fatty tissues and other healthy cells.
The advantage of the now-banned radio-wave device, he said, is that only during initial treatments are temperature probes needed to determine what level of heat is best for individual patients. Studies have shown that once that level has been established, it will remain fairly consistent throughout the patient’s treatment, he said.
According to both Storm and Morton, the FDA’s insistence on repeated temperature monitoring with the radio-wave system is as dangerous as it is unnecessary.
“These are pre-terminal patients, many of whom have life expectancies of three to six months,” Morton said. “We are being asked to place temperature probes the size of pencil leads inside their organs on a daily basis. . . . It’s just not practical. . . . Nor is it humane. . . . Maybe you could collect some interesting scientific data by doing it the way FDA wants it done . . . but it’s no way to treat patients.”
“It think it is a terrible crime,” said Henry, who joined the project after receiving treatment himself at UCLA for cancer 11 years ago. “These are people, I think, who are here today who wouldn’t be here if they had not received this treatment. . . .
“The FDA has a closed mind on this, and we haven’t been able to figure out how to open it.”