Enter the cancer wards of Miami in January 1981.
Behind the door of Room 2015 is Carol Silvani, a model whose career ended when she lost one breast to cancer. She has already tried an experimental drug in an unsuccessful attempt to beat the cancer. Now, at age 40, she is thinking that she should forget about the drugs and just go home and die as peacefully as possible. "I've been through too much," she says.
On another floor, behind another hospital door, Ann Laurie is being comforted by her daughter. The socialite and golfer, age 56, is still trying to forget the hallucination of death brought on by an experimental drug. "I'm doing a lot of praying," she says. "I'm relying more on God than on drugs."
In another room is Jerry McClennan, 41, a newspaper delivery man. McClennan, who was made "deathly ill" by an experimental drug used in an effort to fight his lung cancer, has made a vow to his wife. "I damn sure don't feel like no guinea pig," he says. "I'm gonna beat it. I'm gonna live."
Ten months later, they are all dead.
Silvani, Laurie and McClennan died of cancer earlier this year, leaving behind families, medical files, charts of experiments and another kind of legacy: their own views of the world that exists inside an experimental cancer clinic.
The Miami clinic, officially known as the Comprehensive Cancer Center of the State of Florida, is one of 20 major cancer centers in the United States. What has happened there is similar to what goes on in institutions around the country for tens of thousands of patients who have been given experimental drugs under the sponsorship of the National Cancer Institute. It is a world of disappointment and poor therapeutic results, but always there is the hope of something better to come.
Here are the stories of the patients, families, doctors and nurses at the Miami clinic, told in their words, from their perspectives.
In March 1980, Jerry McClennan's cough took a turn for the worse. He lost his "taste for cigarettes." A friend told him to get a chest X-ray and he took the advice. Later, he would recall that day.
"When that goddamned doctor came out, he didn't waste no words. 'You got cancer in both lungs,' he said. 'You ain't got long at all.' I was 41 years old. It could make your knees buckle with a sentence like that."
Within weeks, McClennan began standard chemotherapy treatment. He would remember the intravenous needle injected into his hand and the nausea that followed. He would remember running to the bathroom at night and vomiting for five hours, sleeping through most of the day because he had no strength.
And he would remember that the drugs did not work. A nurse at the Veteran's Administration Hospital in Miami told him as much in December 1980. "Jerry," said the nurse, "honestly, this drug is not giving us the results we want."
A doctor examined him and then left the room "mumbling" something to the nurse. A moment later, the doctor returned and told him he should try a new drug. That medicine was ICRF-187, an experimental drug.
McClennan signed a required informed consent form allowing his participation in the drug experiment.
"I'll tell you the truth," McClennan said later. "I read the thing and I was scared to death. I didn't want to do it, but it was either go on this or nothing. The reason I did it was for one man, the doctor with the goatee. He suggested it and I think he knows his business. He's educated. I felt this guy was a good schoolboy who had done his homework and that this was a drug that could knock this. I figured he wouldn't be in that position if he didn't have knowledge."
McClennan thus became part of a Phase I study, an experiment whose main purpose is not to treat the cancer, but to observe the side effects of the drug and to establish the proper dose to be used in further tests. But at the time, McClennan did not understand any of that.
He began taking ICRF on Jan. 8, 1981. His third dose came on Jan. 22. The next day, he said: "It ran into me for 12 minutes. I felt woozy. I could feel my temperature rise . Two hours later, I could feel it here in my heart."
McClennan said he slept for several hours bundled in an overcoat and blanket. He awoke shivering. Again he went to sleep for several hours. "I woke up sweating. My clothes were steamy. I was wringing wet," he recalled. "It made me deathly sick . . . . You just plain feel miserable all over. Your limbs, head, eyes, your mouth, your big toe even. I don't know how you would describe it."
A day later, he said he was feeling better, but still a bit drowsy. "If these drugs don't help, I'm going on natural foods, that's for sure. Cause, by God, I'm gonna beat it. I'm gonna live."
McClennan was asked whether he understood the purpose of the experiment. "I seen something about a Phase I in there," he said. "Does that mean anything?" He said he would not have gone into the experiment if he felt its main purpose was to find side effects and dose levels.
"I damn sure don't feel like no guinea pig," he said. "I'm mostly worried about myself. I'm 41 years old and I've got a hell of a lot of things in life to do. I'm young and I'm strong and I don't want to go."
His wife, Christine, said of the experiment: "I'm for it if it works. But see, I've gone through this before. My father died of cancer.
"All they're doing is killing you quicker," she then said of the experimental drug.
Three weeks ago, at 1:45 on the morning of Sept. 30, Jerry McClennan died at Miami Veteran's Administration Hospital, the same hospital where Christine's father had died seven years earlier.
'You'll Try Anything'
"For some reason, I've always had all the faith in the world in doctors. If they told me to stand on my head, I would."
Ann Laurie was a wealthy woman, a socialite and golfer, who lived in Palm Beach. She spoke about her experiences with experimental drugs during a visit to the Miami clinic last Jan. 13. She said she learned she had breast cancer in 1974. She had a mastectomy, but the cancer had already spread. She had tried several commercial anticancer drugs, but none of them worked. So, in 1980, she began taking experimental drugs at the cancer center in Miami.
The first experimental drug she tried was a hormonal drug called AG (aminoglutethimide).
"It wasn't on the market, but it had worked for other people," she said. "They asked me if I wanted to experiment, and I said yes."
Within days of taking AG, Ann Laurie became sick.
"It was terrible," she said. "I lost my appetite. They sent in beautiful steaks. I took one look at them and hid them. I was sick, with dry heaves, nausea, tired. I was sad, I was blue, I was unhappy. I felt like nobody loved me."
"Depression," interjected her daughter, Jeanne Ann. "That was the worst thing in the world with that drug. She was crying all the time."
"There were no signs that it was working," continued Laurie. "But I never considered going off it. This went on for four months . . . . Why? Because the doctor said it takes that long to find out if it works."
On Dec. 10, 1980, Ann Laurie went off AG. She recalled that her doctor, Charles Vogel, told her: "The AG isn't working. We have a new thing that's not on the market yet, and we'd like you to try it."
This second experimental drug was called Provera. She agreed to take it. "When you're desperate," she reasoned later, "you'll try anything."
The tests with the new drug began that same day, according to clinic records. Here is how Ann Laurie remembered it: "I had a splitting headache. I was throwing up. I was seeing lights. I'd never believe I would have gone through something like that . . . . I was scared to death. I thought I was dying . . . . I saw lights and thought, 'This is it.' Pains that were so horrible that you couldn't stand it. In the head -- oh, sharp pains."
The intense suffering lasted for almost three days. Then she stopped taking the drug and felt fine within hours. Perhaps, she was told, she started the new drug too soon after stopping the first one. Perhaps the combination of the two created the severe side effects.
"I'm doing a lot of praying. I'm relying more on God than on drugs," Laurie said later. "I'm taking them because I think somebody's smarter than I am -- that he's studied this for a long time."
She paused, going over in her mind what she had just said about her trust in cancer doctors. "I've thought about that a lot. Do they know what the hell they are doing?"
One month later, at Good Samaritan Hospital in West Palm Beach, Ann Laurie died of cancer.
'How Do You Go?'
Carol Silvani was a Miami model who, as she put it, "wanted to set the world on fire." But in 1977, at age 37, she learned she had breast cancer and had a mastectomy.
"The first thing I would tell you is that cancer is the worst thing that ever happened to me and the best thing," she said last Jan. 12 from her hospital bed. She said that before she had cancer, she was always active, always tense, never devoting enough time to her family.
"My outlook on life is so much more casual now," she said. "You don't let little things bother you anymore. I don't panic anymore. I always used to be in such a rush. There's something to the adage: Live each day as if it's your last."
That new, more reflective, outlook carried over to how Carol Silvani made her decisions for treating her cancer, which had spread and now appeared terminal. Her doctor, Charles Vogel, and a nurse, Dawn East, said that Silvani asked more questions about her treatment than most patients. Among the questions she struggled with was whether no treatment was better than toxic drugs as the end approached.
"With cancer, you know, none of us know from second to second," she said. "The main thing is that nobody comes out of this alive. The question is: How do you go?"
She had tried many drugs in the past, some of which seemed to do some good against her cancer, but none that could cure her. And there were the side effects: "I've been through so much crap. I lost my hair twice. I've vomited for nine weeks at a time -- without eating at all, except swallowing jello and throwing it up again."
For five months in 1980, she had taken an experimental drug called AG. Now on Jan. 12, 1981, Vogel was suggesting another possible experimental drug -- Provera. She was deciding whether to take it.
"Basically, I'm not going to question it," she said, "because I saw a positive look in his Vogel's eyes . . . . Now, it's like if they have anything that even has the slightest chance, I will try it."
As she spoke, Silvani still had the hope of a cure. "I want to be a real together woman of 55," she said. "I don't want to lose the thrill of seeing my kids grow up."
The next day, she signed the informed consent form authorizing the start of the experimental drug. Within days, her diagnosis grew seriously worse. Her cancer had spread to her central nervous system. Vogel told her she had these options: to continue to try to fight the cancer with various therapies or to stop treatment altogether. On Jan. 20, Silvani made her decision and told Vogel, who supported it.
"Carol just decided it's time to die," the doctor said after leaving her room. "She's going off all therapy and going home."
"I've been through too much," Silvani said on a day when she believed she had two months to live. "Dr. Vogel said he'd do the same thing . . . . Medically, I know there's no future. They can put me back in remission, but then it will come back. I don't want to get better just so I can get worse again. I was up all night long, throwing up. And I'm still fighting. You fight like hell with the medical treatment, but then you also have to fight like hell with your spirit. My calmness is probably a much better treatment than anything else at this point."
On Jan. 23, she checked out of the hospital and went home. She felt better for about a month, even going out with friends once and "dancing till 2:30 in the morning."
Two months later, she was back in the hospital. The final entry in her patient file says: "Throughout patient was sedated. She only responded to her name. When awake she did ask for pain medication. On 3/18 patient expired 1:12 p.m."
'A Human Dog Lab'
In the study of experimental anticancer drugs, Harvey Mottaz might be considered something of a success story. Mottaz, 64, had a "partial response" to the experimental drug ICRF-187 that lasted 69 days, according to records of the experiment.
But on the morning of Jan. 15, 1981, one week after going off the drug, Harvey Mottaz was resting in his bed at Miami's VA Hospital, and he looked like anything but a medical success story. After surgery, radiation, standard chemotherapy and experimental drugs, the cancer was still eating away at his neck and face, which looked more like a skull.
The day before he had been given more chemotherapy. He was resting now, and his speech was slurred. He was unable to tell his own story. He reached for a pen and scribbled "Call my boy -- Ft. Myers."
Mottaz was 150 miles from his rural home in Alva, where he made a living sanding wood floors. His wife, Jewell, recalled the effects of the experimental drug. "They tried some new treatments and medicines on him," she said. "It didn't do him any good. It made him sick in the stomach and made him throw up. It made him sick all over. His hair fell out."
Ted Feldman, who had finished Harvard Medical School a year earlier, was an intern at the Miami hospital, attending Mottaz and other patients. This is what he had to say about the drug experiments and the infusion of drugs Mottaz was receiving:
"It's a human dog lab. In his case, it's just witchcraft. We blasted hell out of him yesterday. Any normal person like you or me, it would have turned our livers to mush. I can tell you if it were me lying there, I would have killed myself."
Harvey Mottaz died on July 27, 1981, at Lee Memorial Hospital in Fort Myers.
Charles Vogel, 43, is the director of the experimental clinic at the Comprehensive Cancer Center in Miami. He, like most cancer doctors, is engulfed in a world of strong emotions, high pressure, constant uncertainty and constant distress -- with patients routinely dying of the disease and often becoming sick from the treatments.
His patients and his staff describe him as compassionate, meticulous and, above all, honest.
Vogel fully supports the national drug development program and the experiments on his patients. But if he had an incurable cancer himself, he says, he would not take part in a drug experiment.
"I have my own views of life and death and how I would handle myself . . . . If I reached the stage in a terminal illness and had exhausted the useful agents drugs , it's hard to say what I would do. But I wouldn't be subjecting myself to toxic therapies."
What would he do?
The first answer: "I'd travel a lot . . . . I'd go fishing."
The second: "I'd kill myself."
But Vogel tells his patients none of this when they are deciding for themselves whether to take experimental drugs. He says it would be irresponsible to express such personal views, that it is not his job or even his right to do so.
"Is it really the doctor's role to take away their hope?" he asked during an interview. "To go in and tell them day after day after day that the likelihood is it the experimental drug isn't going to work?"
Vogel said he tells every patient about the possible side effects of the drugs and about what he calls their "very, very low" chance of success. But in their desperation, he says, terminal cancer patients want to try something, anything.
"With all that's in the informed consent forms, it's a wonder that anyone goes on any investigational regimen experimental drug ," he said. "We're honest with these people, and in spite of our honesty they go ahead . . . . If there's anything, they'll try it."
In a sense, Vogel is more fortunate than many cancer doctors. He specializes in treating breast cancer, which is curable in two-thirds of the cases. But his clinic routinely gives experimental drugs to incurable cancer patients, and the results have been similar to those around the country.
"Of the ones I've investigated, most of them have been busts, unfortunately," Vogel said. "It hasn't been overwhelmingly successful."
Still, he remains optimistic. "If I weren't," he said, "it would be very difficult to stay in this field."
Dawn East, 26, has been a research nurse at the Miami clinic for more than four years. She sees her primary role not as trying to help cure cancer patients, but rather as helping to make them more comfortable in their last days.
"In medicine, the object seems to be cure, cure, cure," she said. "But when you're dealing with the terminal cancer patient, it's very different -- it's much more personal. I help people die. And dying is as much a part of life as anything."
Experimental drugs, East said, in a way, help her do her job. "One thing it an experimental drug gives the patient is a relationship with a research nurse when they're becoming terminal," she said. "They have somebody who cares -- only because they are on a study."
She said she wants patients to make up their own minds about whether to take part in the drug experiments, but she is well aware that many patients depend on her or the doctor. "These people tend to rely on you so much," she said. "If you say, 'Stand in the middle of the expressway,' six out of 10 will do it."
East also pointed out that some of her patients automatically associate her with chemotherapy and its side effects. "I have a standard joke," she said. "Every time my patients see me, they get nauseous."
From the start, the experimental drug called IMPY offered very little hope. Mary Wolpert, who reviews animal test data for all potential anticancer drugs at the National Cancer Institute, said she felt it was one of the least promising experimental drugs ever put into clinical tests.
Moreover, a study conducted by the Institute Jules Bordet in Brussels in 1966 with 22 people concluded that IMPY "failed to display any therapeutic activity."
Three years ago, the National Cancer Institute chose to reexamine the drug. It opened its own studies at five hospitals in the United States beginning in 1978. Over the next two years, 132 patients were given the drug. The Miami clinic run by Dr. Vogel used IMPY in its main experimental drug study during that time. In Miami and elsewhere, there were no complete or partial responses, according to an NCI report of June 1980, which led to the end of IMPY tests.
The drug was found to cause nausea, vomiting, central nervous system disorders ranging from confusion to psychosis, and destruction of red blood cells -- a condition that was fatal to one patient in Texas. The damage to red cells forced nine patients at the Miami clinic to receive blood transfusions.
For any study to be of value to the National Cancer Institute and patients who might receive an experimental drug, the study must be meticulously monitored and recorded. That was far from the case with IMPY in Miami. A review of the records reveals a variety of inaccuracies, lost reports and forms, and laboratory work that simply was not done.
Dates of death of patients receiving IMPY recorded in hospital medical files in some cases differed from the dates on the Dade County records by months. For example, the Miami clinic files record the death of Robert Wallace as June 10, 1978. In fact, according to his death certificate, he died more than three months later. There are several similar disparities.
Darlene Padgett, the research nurse who kept IMPY records for the clinic, said she was responsible for the errors:
"I would hear from the grapevine that a patient died. I wasn't about to call up the wife and ask her for the date. I couldn't do that. Hearsay would be the best I could do on a death . . . . It seemed like such a small thing. When they died didn't seem that important. That they died, that was important."
Some critical lab tests were not performed, according to the clinic's records. Liver and kidney function tests, required by the terms of the experiment, were not conducted as they were supposed to have been on Jonas Karpavicius on Oct. 10, 1978. A few weeks later, that same patient's chart notes: "Comedy of errors!! Blood not drawn -- after all it was a Sunday . . . lab refused to draw."
The file for patient Julius Brown noted: "VA lost chart." That, director Vogel explained later, meant Brown's entire medical record could not be found, at least for a time. The record for patient Earl Owen noted that the results of a Coombs test for immune reaction were "negative." But the medical file of that same day says the "Coombs test was lost due to lab errors."
'Can Do No Wrong'
Nokomas Dirkes was one of eight patients at the Miami clinic who received the highest dose of IMPY -- a dose so high that many of her red blood cells were destroyed, forcing her to be hospitalized for a transfusion. The drug did not help her cancer. She died on Sept. 3, 1979, at age 64.
Her nephew, Douglas Lovely, who runs a marine construction business in Miami, is still angry and upset that his aunt was in a human experiment that made her sick but did not help her. It was he who signed the informed consent form allowing Dierkes to go on the experiment.
"I haven't the faintest idea what the experiment was about," he said. "I'm not really sure my aunt understood what they were doing. And this is what made me really angry. I was very upset myself. There was so much of the medical terminology that I couldn't understand. It seemed like they were giving us Latin words and so on. They could have told me they were feeding her snakes at the time -- I wouldn't have known."
Lovely said his aunt had pelvic cancer and was afraid she might have her legs amputated. "I told her, 'Aunt Nikki, do you understand what you're doing? They can do anything they want to you.' And she said, 'Just as long as they don't cut off my legs.' "
He recalled that the experimental drug made her so sick that she had to be hospitalized. "She got very ill," he said. "She was nauseous and throwing up, had pain everywhere. She was dizzy. She was in and out of the hospital."
Up until that point, according to Lovely, the whole family, especially his aunt, had total confidence in the doctors. "She had a very trusting attitude up to that point," Lovely said of his aunt. "But along there at some point she just did a flip-flop about her trust in doctors. In the beginning, I had the same view: 'Doctors can do no wrong.' Since then, these people to me are, well, they're not people as I know people."
Lovely said he now feels his family made the wrong decision in allowing his aunt to go on the study.
"I wouldn't take those drugs," he said. "Even if I had some iota of a chance, I wouldn't do it. Knowing what my aunt went through, and the others, and the people who came to visit them . . . she shouldn't have ever gone through any of those horrible treatments."
"It was supposed to be something new," Ann Melcher recalled of the experimental drug IMPY. She knew her husband, William, was running out of choices, having gone through surgery, radiation and standard chemotherapy without being able to stop the cancer that began in his sweat glands and now was gnawing at his lungs.
"He had no other alternatives," said Mrs. Melcher, a nurse. "I told him, 'The decision is yours.' "
William Melcher, a 52-year-old funeral director in Miami, read the informed consent form for the experiment and decided on July 20, 1978, to begin taking the experimental drug. "Everything that was known about the drug was written down," recalled Mrs. Melcher. "But both of us realized there was absolutely no cure."
Clinical records of the experiment note Melcher's reaction to the drug. He lost his appetite, began losing weight, had diarrhea, and showed signs that his liver was malfunctioning. And his wife noticed more profound changes:
"It did nothing good," she said. "It seemed like it was just downhill after that. His whole system just collapsed; his kidneys, just everything collapsed. He even got a heart problem and swelling and edema fluid in the lungs after that . . . . I thought in retrospect it was useless."
She continued: "I don't think anyone can draw the line between the course of the disease and the effect of the medication. I really wonder if anybody knows. I really don't think the doctors know. That may sound cynical, but I'm sure they don't understand cancer. I think they are poking blindly. They say they are finding cures. I wonder if they are not mistaking them for remissions."
At 8:05 on the morning of Sept. 7, 1978, seven weeks after going on the experimental drug, William Melcher died.
'I Was So Angry'
"I didn't think it was a miracle drug, but I did think it had a chance," said Darlene Padgett, a research nurse at the Miami clinic who worked on the IMPY experiment. "I think I was pretty idealistic. I thought, 'This is a new drug. It's been successful in animals' . . . It was the great humanitarian in me. I felt hopeful, really very hopeful."
The hope was soon dashed.
"As we used the drug more and more," Padgett recalled, "it became evident that it wasn't really helping them. You could see the tumors continue to grow as they got the drug."
It became equally clear to many of the patients that the drug was not working. "I had patients who knew they were going to die. They asked if I thought it would be all right to go to another state. I said, 'Sure, go catch trout up there.' "
One by one the patients died, many of them within weeks of beginning the experiment. "How well do you cope with their dying? Sometimes very well, sometimes not very well," said Padgett. "You care enough to cry for them. You cry sometimes without even knowing it. And there was the futility of your caring."
Padgett said she had a profound sadness after the IMPY experience, a sadness which she shared with Vogel and others on the staff. "We had to talk about it. You couldn't cope with it individually," she said. But sadness was not her only emotion.
"I was so angry. It was like you just want to lash out at someone. You can call the drug people any name you want to. You can stomp your foot. I can remember being so angry and disillusioned and thinking, 'What's wrong with these people who invent these drugs? Can't they do a better job? Can't they be more precise?' It's indirectly directed at everyone and everything. When you deal with something like cancer, who do you direct your anger at? God?"
'Super Guinea Pig'
Margaretha Gaylord, 47, had a malignant melanoma, which is usually incurable, when she stepped into her doctor's office last Jan. 16. She had already tried several anticancer drugs, but none of them worked. She knew that her doctor, Michael Troner, was going to ask her to take part in a Phase I study -- the first time humans would be given a drug called ICRF-187.
She was in good spirits that day when she and her husband Bill stepped into Troner's office, despite her prognosis. "Well, let's get on with it, Doc," she said.
"You know the tumor did not respond" to other drugs, Troner told her, beginning the required informed consent session. "And it's obviously growing. What I want to do is use some drugs that hopefully will work . . . .I would prefer at this point to use some investigational drugs."
He told her that side effects in other patients on the study had to that point been minimal. He said she would have to come in every week for examinations of her blood and other vital functions. He said she might lose her hair during the study. Then he concluded: "I would like to put you on the drug. What I want you to do is read the informed consent, and what you don't understand, Renee Troner's assistant and I will explain to you."
Gaylord quickly read through the form. She looked up and said, referring to the dose schedule: "Well, I get a two-week rest period. That's nice."
"Do you have any questions?" asked Troner.
"Well, you know, it's just about the same as all the others," responded Gaylord.
Then she joked about the possibility that her hair might fall out as a result of the drug. "I always wanted to be a swinging blonde. So I'll get a wig."
Troner then handed her a copy of New Yorker magazine, upon which she placed the informed consent form on her lap. She signed it, looked up with a smile, and said, "Well, there I am -- super guinea pig once again. I've tested just about everything."
She began taking the experimental drug.
It did not work.
Six weeks later, on March 1, Margaretha Gaylord died of cancer.
The 'Can-Do' Attitude
Doctors say that their patients often fail to understand what the drug experiments are all about.
"The patients are so anxious to grasp at the possibility of hope that sometimes they don't understand what we say," said Troner, who treats patients at his Miami office. "All the patient wants to hear is 'Do I have a shot? Do I have a chance that the drug will work?' And I really think that that's all the patients are hearing. You can tell them all the mumbo-jumbo in the world . . . . But they won't hear most of what you say."
Troner supports the experimental drug program -- "I would rather treat them and go down fighting with them than ignore them," he said. "I know sometimes we even make them sicker by treating them. But I'd rather try than pat them on the back and tell them to go into the corner and die."
Still, Troner acknowledges that most of the drugs "will probably be bombs." He offered another reason why the experiments continue:
"It's just so obvious that the reason we do these things in America is because we're expected to. And the reason we're expected to is because of the people in this country. The more I see my patients, the more I see how Americans react to medicine and illness. Americans have the 'can-do' attitude. They expect the best. And their understanding of the best is that we should be able to do miracles."