The treatment takes three weeks and is given in the intensive-care unit, Kevin Fox said, because it's a new type of drug and may precipitate a heart attack or shock or respiratory failure.
Fox told Mark that he would become nauseous, lose his appetite and have diarrhea. His skin would become very dry and start itching terribly and peel like a bad sunburn. Some patients, Fox said, literally go crazy - they don't know where they are and lose contact with the world - but this lasts for only a little while.
"It seems like a long run for a short slide," Fox said, studying the patient sitting before him, chewing gum. "Doing nothing at this point is just as reasonable as doing this." Fox's voice was much softer now, less clinical than before. Mark stopped chewing and shook his head with a frown.
"There's no doubt in my mind," he said. "I'm going to do it."
Every year 25,000 cancer patients enter federally sponsored programs to test new cancer treatments.
The vast majority of trials are much less risky and frightening than the one Tim Mark was about to enter, usually involving nothing more daring than testing a slight variation on the current treatment of choice.
But for several hundred of these patients there is no treatment of choice
because nothing works against the type of cancer they have. These are the patients who take great risks because the alternative is certain death. These are the patients who are the first to submit to the newest discoveries from the basic research laboratories. These are the shock troops of clinical research.
Tim had malignant melanoma, a cancer of the pigment-producing cells in the skin. Caught early, the cancer is curable with surgery in 100 percent of cases. Caught late, after the cancer has spread to other organs in the body, it is 100 percent fatal. Tim's cancer had already spread. Three rounds of surgery and conventional chemotherapy had not worked, and nodules about the
size of dimes were growing behind his kidneys and in his lung.
Penn was experimenting with a new type of drug called IL-2 (interleuken-2). Discovered only a decade ago, IL-2 is a biochemical normally produced by the body to help fight off disease, possibly including cancer. IL-2 is an integral part of the immune system. It activates white blood cells, called lymphocytes, preparing them to attack and kill disease in the body.
Doctors reasoned that if a little IL-2, manufactured by the immune system, is effective in controlling some diseases, then a lot of IL-2 manufactured in the laboratory and injected into cancer patients may help them win the battle against cancer.
First tried in humans only five years ago, this so-called biologic therapy offers a totally new approach in fighting cancer. Some researchers believe it will revolutionize cancer treatment because unlike conventional drugs, which kill healthy cells as well as the cancer, biologic therapy, when perfected, should attack only the tumors.
Despite a torrent of publicity surrounding the first IL-2 announcements, so far the drug has been effective against only malignant melanoma and kidney cancer, and even with these cancers the success has been modest. Long-term, complete remission, in which the cancer is eliminated for good, has been achieved in only 5 percent of patients.
Almost as many patients - up to 3 percent in some centers - are killed by the treatment itself.
Scientists point out that the clinical research is just beginning and that much more must be done before this becomes a standard form of treatment.
If biologic therapy achieves the potential seen for it, much will be written about the doctors and all the patients they save. Little will be said about those patients who underwent therapy in the first stages of development, before it was reliable, safe and effective.
Tim was admitted to the intensive-care unit of the University of Pennsylvania Medical Center on Monday, April 10. It was almost exactly two years since the day that Tim's girlfriend, Joyce Luckenbill, discovered the mole on his back.
Tim was put into a private room filled with high-technology equipment and monitoring devices. Beside the bed was a ventilator, should he lose the ability to breathe on his own. IV poles lined the bed on either side, and overhead was a digital readout that would keep medical personnel constantly informed on his respiration, blood pressure and EKG.
Radiologists had just taken CAT scans (three dimensional X-rays) of Tim's melanomas. They would be compared with a second set of scans taken in seven weeks to see if the treatment shrunk the tumors.
Climbing into bed and submitting to the routine of the ICU, Tim wondered if the nodules had gotten any bigger. He knew that some melanomas remain dormant for months, sometimes a year or more, before springing back to life and killing their host.
Others grow very rapidly, without stopping, and kill within a few months. He realized that the radiologist who had just taken the CAT scans probably knew what type of melanoma he had.
Linda Podell, a young nurse with very large eyes, dark hair and self- assured manner, came into the room, introduced herself as Tim's primary nurse and started describing what would be done. But her serious tone bothered Tim, so he tried to lighten the mood by teasing the nurse about the high-tech equipment and her ability to keep him alive once therapy got under way.
Tim didn't want to think about all that he was about to go through; he tried instead to think about the saplings he had planted just before coming into the hospital. He had put in five trees around the house he shared with his mother, Helen Mark, on East South Avenue in Glenolden.
He thought about his latest painting - a watercolor of a string of geese standing in a field, looking very alert, as though they had heard a suspicious sound. Titled Ever Watchful, the painting had become very important to Tim - almost a rite of passage, from amateur to professional artist.
Tim was having 1,000 prints made of the painting, which he was advertising in the August issue of Country Sampler, a decorating magazine, with the hopes of selling them all to an eager and appreciative public. Tim had been making his living as an actuary in an insurance company, but at heart he was really an artist.
Tim looked up at the digital readout over his head and the numbers that represented his pulse and respiration.
He was outraged that his life should be cut short by these damn little things growing inside his body. The nodules had become Tim's enemy, and his response to them was now an all-out war.
Tim said that he didn't expect to win this war, but that it was very important that he wage it - even though it meant he would have to spend much of the little time he had left anticipating, enduring and recovering from the harsh experimental therapy.
"I hate needles, but I don't hate needles so much that I want to let this cancer win without a fight. . . . When I'm on the other side," he said, referring to his own death, "I want to be able to say I did everything I could."
Tim looked through the glass wall of his room at the doctors' and nurses' station outside. How fast is the cancer growing? What did the CAT scan show? The black thoughts were coming back again and Tim didn't like it.
Reaching for his wristwatch and setting the timer, Tim took a gulp of air and held his breath, triggering the alarm over his bed. Podell came rushing in.
"Twenty seconds," Tim said, consulting his watch. Podell didn't seem amused.
David Grossman, a cancer fellow and one of Kevin Fox's assistants, came into the room and asked Tim if he was comfortable.
Have you seen the CAT scan? Tim asked. Grossman said that he had.
Is the cancer growing? Tim asked.
Grossman admitted that the nodules seemed to be a little larger, but that it was difficult to say for sure because the two sets of pictures were taken with different machines. If they are growing, they're growing very slowly, Grossman said.
"But there is progression?" Tim persisted.
Tim became quiet. Grossman waited to answer more questions, but Tim said nothing so Grossman left. Tim was so shaken by the news that he had forgotten to follow up with the obvious question. It wasn't until almost an hour later that Tim was able to put the carefully worded question to Kevin, when he stopped by to say goodnight.
Explaining what Grossman had told him about the CAT scan, Tim asked:
"If the cancer continues growing at this rate, how much time do I have?"
"About a year," Kevin said.
When patients enter risky experimental trials, such as the IL-2 program, researchers are usually very frank about the bad odds, and most patients say they understand this.
"Patients may tell you intellectually that they know there's no hope, but deep down, underneath, they think there's a shred of hope and that's what they hold on to," said Barrie R. Cassileth, director of psychological research at Penn's Cancer Center.
Cassileth has done studies on why patients participate in such trials and what they expect from different types of treatments, and she has concluded that it is easier for people to go through risky and often ineffective treatment than to do nothing.
"It's very uncomfortable for patients to do nothing," Cassileth said. ''It is part of the American spirit. In this country we fight and we strive. . . . It is a culturally ingrained reaction in the vast majority of patients to do something even if there is no hope that something will come of it."
Cassileth agreed that the need to do something makes terminally ill patients vulnerable to zealous researchers, but she said she did not think patients were being taken advantage of.
"Even if you tell patients there is nothing more that can be done, they will go out and find something on their own," Cassileth said.
Robert J. Levine, a bioethicist and professor of medicine at Yale Medical School in New Haven, not only believes that doctors should provide terminally ill patients with the possibility of even unlikely remedies, but he also thinks it would be unethical for them not to.
"The most unethical thing a researcher can do," Levine said, "is to deprive (the terminally ill) of not only the opportunity but the responsibility to make choices."
However, he said, researchers must help patients make reasonable decisions by giving them all the available information and "tempering their enthusiasm when it seems to be overly optimistic." He thinks institutional review boards set up by medical centers to scrutinize experiments involving human subjects have been an adequate safeguard.
Kevin said that at Penn only 5 percent of patients inquiring about IL-2 therapy decide against it, even after being told how difficult the treatment will be.
Kevin's assistant, Mary Dee McEvoy, who holds a doctorate in nursing and has studied what goes through the minds of patients entering experimental studies, said it's impossible to prepare a patient fully for these experiments. Pain and fear are very subjective, she said, and patients must make their own decisions.
Her study showed that patients constantly re-evaluate their original decision to undergo the treatment in response to changing symptoms and side- effects, but most choose to continue. Only two of the 16 IL-2 patients treated at Penn quit the study because they couldn't take the side-effects.
Tim was hit with a fever of 102.4 and shaking chills four hours after receiving the first dose of IL-2 on Tuesday. Nurses wrapped him in blankets, and three hours later it was over. Tim said it wasn't so bad.
The next afternoon, having made it through the first onslaught of side- effects, Tim seemed to be in a particularly good mood and started barraging the new nurse on duty with jokes and teasing comments.
Working on the chart at the foot of the bed, Joyce Townley fended off the jokes and then, when Tim became quiet, asked him what he was expecting to happen over the next few days.
A lot more chills, he said, and he expected to feel nauseous and to get diarrhea and have terrible itching. His skin was already becoming flushed from the first dose of the drugs.
"So you're waiting around here for all of that to happen?" she said.
"Yes," Tim said, momentarily serious, but then he began again with the joking. He kept at it for several minutes and then became quiet again. Townley said she could imagine what he was going through.
"I joke a lot and make sarcastic comments when I'm nervous," Townley said quietly, going to the door.
"I have to go now to take care of someone in the next room," she said. ''But I can come back later and we can talk, if you want."
That night Tim got hit with more chills from the IL-2 and was shaking badly when Kevin came in to see him.
Seven years younger than Tim, Kevin is a large, good-natured man with red hair, freckles and glasses. He looks much more like a friendly GP than a remote, highly specialized, academic physician.
"You're doing great," Kevin said, consulting the chart near Tim's bed. ''You're right on schedule."
Tim was still wrapped up in blankets, pulled tight to his chin, when his mother, his sister Anita Reynolds, and his girlfriend Joyce arrived to see him that evening. They tried to make small talk and bring him up to date on what was happening back home, but Tim was too sick to respond.
Flu-like symptoms developed the next day, on Thursday, the third day of therapy.
The curtain had been drawn against the bright sunlight and the room was softly lit. Tim had lost his appetite and was beginning to throw up. He spent most of the time now trying to sleep, not just because of the drugs, but from the exhaustion of life in an ICU.
The nurses were waking him up every four hours to give him drugs by mouth and they were coming in every 30 minutes to see that he was all right.
On Friday Tim's blood pressure dropped sharply and fluids had to be pumped into his circulation to keep the pressure up. Also his kidneys had almost stopped making urine, requiring other drugs to help get rid of the fluids.
Concerned about these problems, the doctors let him miss some of the doses of IL-2, rather than risk complications that couldn't be corrected.
Tim was beginning to wonder if it was really necessary to get every dose and questioned whether it made any sense to be going through all this. But always he ended up deciding that this was what he must do and then braced for the next dose of drugs.
Finally, on Saturday, it was all over - at least the first phase of the IL- 2 therapy was completed - and Tim was given a week of rest in the intermediary intensive-care unit while lymphocytes from his blood were harvested to be used in the second stage of his treatment.
So far Tim had done very well. He had received 12 of 14 scheduled doses with no serious problems. No patient had ever gotten the full schedule of drugs at Penn, the therapy is so difficult.
The second phase of treatment called for mixing Tim's lymphocytes with IL-2 in the laboratory and then injecting the treated white blood cells into his body. Doctors didn't know, however, if this would make any difference. Answering this question was the main goal of the research being done at Penn and 11 other centers cooperating in a national study.
The theory was that if IL-2 could activate lymphocytes when injected into the patient's circulation, then it might work even better when mixed directly with lymphocytes in the laboratory. Theoretically it should turn the lymphocytes into very potent LAK cells (lymphokine-activated killer cells), primed and ready to wipe out any cancer cell they come across when injected into the patient.
But preliminary studies with humans have been disappointing, and researchers might abandon this arm of the treatment, depending on the results of the 12-center study expected next year.
Using LAK in conjunction with IL-2 therapy is only one of a dozen approaches being studied to improve the effectiveness of biologic therapy.
Most of these experiments will probably fail, but one or two treatments might appear slightly more effective than the others and for a while become the treatments of choice, until another, slightly better method displaces it.
It was with such small incremental advances, over a period of three decades, that doctors were able to develop a combination of drugs that has turned pediatric lymphocytic leukemia into a curable disease.
The second round of treatment went without serious incident, though Tim found it more difficult than the first.
Still weak from the IL-2 and exhausted from simply being confined to bed for two weeks, Tim began this phase of his treatment in a much more subdued manner.
He seemed to be turning inward, with the curtains constantly drawn, closing him off from the hallway and the nursing station on one side and the outdoors on the other. He was much too weak to read, and the trivia of commercials made television unbearable.
His mother brought in some of the prints that had been made of Ever Watchful, and doctors and nurses bought five of them. There was even a possibility that one print might be used to decorate a new ICU office. But Tim was too exhausted to enjoy his success.
"I feel tired and run-down," Tim said to a visitor in a voice so weak that it could be barely heard. "Everything aches. My tongue hurts. My muscles hurt. My eyeballs hurt. I'm nauseous."
Again, the thought of quitting the therapy crossed his mind, but that would mean letting the melanoma win, and he had no intention of doing that.
Mary Dee McEvoy stopped by, as she did every day, and stood at the foot of Tim's bed in the dimly lit room, looking at the young man, half propped up in bed, his eyes barely open.
The drugs he had been getting to counteract the shakes and the nausea were making him very sleepy, which was probably just as well.
After studying Tim for several minutes, watching his respiration to see if he was scared or in pain, McEvoy finally spoke, asking him if there was anything she could do for him. He didn't answer.
"Do you have any questions?" she asked softly.
Tim opened his eyes, smiled and weakly offered his hand. She took it. He
closed his eyes and fell off to sleep.
Tim's kidneys kept shutting down during the second round of treatment and his blood pressure kept dropping, so the IL-2 had to be held back several times.
These were the most dangerous medical problems, but for Tim the worst thing was the nausea and the terrible pain in his tongue, made red and swollen by the drugs.
The nausea wouldn't let up. By the final day of treatment, the waves of nausea were coming so often that Tim had no chance to sleep. Hour after hour he sat up in bed with a yellow plastic bowl between his legs, waiting for the next one to hit. His lips were white from the mix of cocaine and Maalox he had been getting to ease the pain in his tongue, and he could barely talk.
Suddenly it came again; he bent over the bowl and tried to vomit. But nothing came up. Breathing heavily from the effort, he leaned back in bed. Another wave swept over him. He bent over the bowl, tried to vomit, nothing came up.
Again and again this was repeated. Then suddenly Tim bolted from his bed to a nearby commode, dragging the IV lines that linked him to the poles around his bed.
It was the diarrhea.
Surprisingly, two days later, on April 28, Tim was able to go home. It was unexpected. He wasn't scheduled to be discharged for another two days and hadn't even thought about leaving the hospital early.
But when he woke that morning and saw the beautiful spring day, the thought struck him.
"What the hell am I doing here when I could be at home?
A little while later, when the doctors came by on rounds, Tim announced that he was ready to go home. They examined him, agreed that he was doing very well and said to go ahead. Tim called his mother and a few hours later was in a car headed home to Glenolden and away from this cursed place.
Many patients are at first frightened to leave the security of the intensive-care unit, but this wasn't the case with Tim. The farther he got
from the hospital, the happier Tim got.
Finally the car drew to a stop in front of his house and Tim got out. He didn't go in at first, but walked around the trees he had planted just before leaving for the hospital. Though he was very weak, Tim took the time to water his trees before going inside.
"There is no question that some patients are living longer because of these treatments," said Steven A. Rosenberg, the researcher at the National Cancer Institute who made worldwide headlines four years ago with the first IL-2 announcements.
One of the first patients Rosenberg treated, a woman given IL-2 for melanoma in November 1984, is still free of disease, Rosenberg said, and dozens of other patients with melanoma and renal cell cancer have been in complete remission, without evidence of cancer, for periods ranging from a few months to a few years.
Rosenberg's team, which has treated more than 300 patients, said that complete and lasting remissions had been achieved in 5 percent of cases, and that an additional 15 to 25 percent of patients had achieved partial remissions, in which the size of the tumors was reduced by 50 percent or more.
Some of these partial responders, Rosenberg said, have remained stable for well over two years, which would have been unlikely with no treatment.
Of the 16 patients that Penn has treated with IL-2 since January 1988, three had to discontinue treatment shortly after starting because of life- threatening complications.
None of the patients died as a result of treatment, but six have since died
from the cancer.
None of Penn's patients had complete remissions, though two had partial responses. One of these patients has since died; the other has been stable, with no tumor growth, for more than a year.
"Obviously many patients do not respond," Rosenberg said, "and some of the responses are not durable, so there's a long way to go. But I think it (IL-2 therapy) represents a start and already is yielding important clinical benefits."
After the excitement of returning home wore off, Tim started thinking about what he would do now, but it was a futile exercise because everything would be determined by the cancer.
If the tumors had been shrunk by more than 50 percent, he'd be classified as a responder and invited to go through the treatment a second time to shrink the cancer even more. And if this second treatment worked, he would be invited back for a third and final treatment. If the cancer hadn't shrunk or if it had gotten bigger, then Tim would have to come up with something else to do.
Only one of Penn's patients had made it through all three rounds of treatment, and even with that his kidney cancer wasn't completely eliminated.
But it would be another month before Tim would know how he'd done, until he returned to Penn for another CAT scan.
During the long weeks of waiting, Tim tried to keep himself busy with his painting and prints, but the concentration was just not there. He was edgy and snapped at people easily. He couldn't sleep, even with the sleeping pills that Kevin had prescribed. He was a lot thinner now - he'd lost 10 pounds during the three weeks of treatment - and his dry skin had gotten so bad that it was peeling off like a bad sunburn. He still couldn't taste food and his throat hurt.
Despite this and regardless of the outcome, Tim said he was happy for having been given a chance to try the IL-2. He said he felt good about having fought the cancer with everything he had and, for a few months, he was spared the terrible feeling of vulnerability that comes from being a victim without options.
Completing therapy, he said, felt like making it through Navy boot camp, or when he finished four years of college in three years because this was the goal he had set for himself.
At times, as he waited for his checkup, Tim was able to be optimistic and said that he thought his chances for a meaningful response were better than 50-50. At other times the hard reality of the statistics hit home and he confronted the fact that only 15 percent of patients responded.
Tim tried to hedge against the unfavorable odds by coming up with a contingency plan should the CAT scan look bad. He had talked to Grossman about another drug, cisplatinum, which when given in extremely high doses might shrink tumors. But cisplatinum is a very harsh chemical and in such high doses causes deafness in 5 percent of patients and a numbness in the extremities. Still he thought it might be worth a try.
When Tim wasn't thinking about the CAT scan or the statistics or alternative treatments, he found himself, from time to time, thinking about death, which hung over everything like a black backdrop. A practicing Catholic, Tim didn't think he would go to hell, but then he wondered how he could compete for heaven against people like Mother Teresa.
And so for more than a month, the heavy emotions and fearful thoughts ricocheted.
Finally the day for the CAT scan arrived and Tim drove back to the hospital.
The technicians greeted Tim with smiles and friendly talk and walked with him to the room with the big machine and a glass-enclosed control room with its panels of video screens and dials and knobs.
They put him on a motorized sled that would slowly carry him into the mouth of the X-ray device - stopping every half inch to give the CAT scan a chance to take a picture of a slice of his torso. Looking for tumors, the radiologists would take pictures of 65 slices, from his throat to his crotch, like carefully slicing through a cookie in search of chocolate chips.
Tim stared up at the ceiling as the technician prepared him for the CAT scan, getting him comfortable on the sled.
"I've got myself geared up to expect that I'll be in the 85 percent
because the law of averages goes like that," he said. "I expect I have six to 12 months to live and that's it. I think it's unrealistic to think otherwise. I have to prepare myself and my family for what we're all going to have to go through."
The CAT scan was activated and slowly the sled advanced into the mouth of the device as the first of 65 pictures was taken.
It took a half hour to finish the series of pictures. Tim's appointment with Kevin and McEvoy was still an hour away, so he went to the hospital cafeteria for breakfast.
While he was eating, the radiologists pored over the pictures, comparing the ones taken this morning with the set taken seven weeks earlier.
All told, 96 little pictures from the two sessions were lined up on the
viewboxes as the radiologists measured the nodules with ruler and caliper.
"Minimal change," the doctor said, finishing one comparison.
"Perhaps it's a little smaller," he said, completing a second one.
"The pelvis looks clear," said a second doctor, looking at the films.
It took no more than a half hour to complete the assessment. The radiologist telephoned Kevin and gave his assessment:
"Multiple lesions. . . . stable in size and number."
Having finished his breakfast, Tim was sitting on the examining table when Kevin strode into the small room.
"There's no change in the lesions," he announced. "It is a tie game." Tim nodded stoically.
Kevin emphasized that this was only the first look, that the study called for a second look on week 11. But after being repeatedly challenged with questions, Kevin finally agreed that rarely did the 11th-week scan look significantly better than the seventh-week scan.
"I figure I have 12 months to live," Tim said. Kevin didn't disagree with him.
Tim told Kevin about his contingency plan, about the high-dose cisplatinum. He said he realized that it might make him deaf and lead to irreversible numbness in his extremities - which could very well end his art career - but he was prepared to go for it.
"Why treat now?" Kevin asked gently.
"Because I still have tumor cells," Tim said. "The melanoma is doing what it wants and when it wants to do it."
Kevin explained that no drugs, other than IL-2, have been shown to alter the course of melanoma or extend a patient's life.
It's true, he said, that some conventional drugs shrink the tumors slightly, but the cancer always starts growing again in a few months. He said there were no data that this shrinkage extended life expectancy or improved the quality of life.
Deciding whether or not to treat is more a philosophical question than a medical one, Kevin said.
"So what you're saying," Tim said, "is that there really isn't any alternative now."
Tim went home and tried again to bury himself in his work, but he was being overwhelmed by increasingly severe fatigue.
Tim wanted to believe that it was a late side-effect of the IL-2 therapy, but he knew that there was another, more ominous explanation - the tumors in his liver were growing again.
Tim tried to ignore the fatigue and force himself to work in his cellar studio. But he kept having to stop. He'd go outside and lie under the little trees he had planted. It was now June and it felt good to feel the summer sun and cooling wind in his face.
Soon the advertisement in Country Sampler would be coming out, and Tim focused on this. August was the time that shops ordered prints for Christmas sales, and Tim was hoping for a strong response to Ever Watchful.
He was convinced that he had the craftsmanship and talent to become an important artist, but he also knew that now he wouldn't live long enough to achieve this. Though he was still trying to paint, he was limiting himself to making improvements on existing paintings.
Since it took an average of six months to do a painting from beginning to end, it didn't make sense to start a new work under the circumstances.
The 11-week CAT scan showed that the melanoma was still stable, but it also hadn't gotten any smaller, so Tim was dropped from the study.
Tim said he was expecting another negative report, but he started sighing a lot after he got the news. Kevin reminded him of the patient who has been stable for 13 months, but Tim immediately pointed out that Kevin wasn't saying anything about all the other patients who hadn't remained stable.
"I don't think this will lie dormant for 13 months," he said. "I believe in miracles, but I don't think I have done anything to deserve one."
Referring a little later to the IL-2 trial, he said "it was Custer's last stand, and the Indians have won."
Still later, he said, "I bought my lottery ticket. I just didn't win."
Even though he was out of the study, he wanted to continue getting the monthly scans. He didn't want this monster that was inside of him to catch him unaware, not like the mole on his back, which he had not noticed until it was too late.
Tim told Kevin about the profound fatigue. Kevin agreed that after so many weeks he should be feeling a lot stronger. But sometimes IL-2 damages the thyroid, and this would cause extreme fatigue. A blood test to check Tim's thyroid was ordered.
Following his meeting with Kevin, Tim had breakfast in a restaurant on the Penn campus. Looking at the young students bustling about, Tim commented on how their lives and careers were stretching before them, just as he was ''getting ready to leave this planet Earth."
Looking back two years to when his girlfriend Joyce found the mole on his back, Tim said:
"When all this started I had all these options." He held his hands wide apart. "Now my options are like this." He brought his thumb and index finger together until they were only a fraction of an inch apart.
A few days later, Kevin called. The blood tests showed that the IL-2 had badly damaged Tim's thyroid. With a prescription for thyroid drugs, he should start regaining his strength.
As predicted, Tim did get stronger, and soon he was working for three or four hours at a stretch on his paintings, but he couldn't do much more than that.
The August issue of Country Sampler came out, but only one print shop inquired about Ever Watchful.
Tim received a letter from his employer saying that because he had been out of work for so long his medical case would have to be reviewed by another doctor to see if he was strong enough to come back to his job.
By the time Tim's next appointment for a CAT scan arrived, he was convinced that the cancer in his lungs had started growing. Describing the pain to Kevin, he pointed to an area near his pectoral muscles.
Kevin shook his head. That's not the type of symptoms you'd get from that, Kevin said. For the first time, Tim bluntly asked Kevin just what the symptoms would be when the cancers started growing again.
If it's the lungs, Kevin said, he'd probably start coughing or be short of breath as the expanding mass closed off air passages. The liver nodule would cause increasing fatigue and loss of appetite. The mass behind the kidneys would cause pain.
And if the melanoma spread to the brain, as it does in 40 percent of cases, he'd probably have headaches and maybe seizures. Once any of these symptoms began, Kevin said, they could talk about the possibility of relieving them with drugs.
"There are a lot worse problems than facing death," Tim said.
"That's a pretty substantial problem," Kevin said.
Kevin asked Tim to lie down on the table and did his routine examination. He felt Tim's liver to see if there had been any growth. He listened to his chest for congestion. And he felt for Tim's kidneys to see if they had been displaced by the cancer.
Since the CAT scan had showed no increase in tumor size, Kevin expected his exam would be negative, and it was.
"Everything is fine," Kevin said, finishing the exam. It seemed like an ironic thing for him to say. Tim said he wanted another CAT scan in four weeks.
"I feel like I have some sort of control by watching it every four weeks," Tim said. "As long as I'm watching it, I can prepare my family. It's better than waking up one day and saying (Tim made a gurgling sound) it's here."
"Some people like it that way," Kevin said. Tim shook his head.
"Have you gotten the print framed yet?" Tim asked, referring to the print of Ever Watchful Kevin had bought. Kevin said his wife hadn't made a decision on the frame yet. Tim nodded, remembering that he had to go to the ICU and pick up prints he had left there for possible sale. No more had been sold, and the doctors had decided not to use any in decorating the new ICU offices.
Tim retrieved the prints and went to the campus restaurant for his usual post-CAT-scan breakfast, even though it was almost lunchtime now. He ordered fried eggs and bacon.
Tim said he and his mother and sister and Joyce had talked about what to do when the time came, and everyone agreed that he should be at home. Someone told him that the local hospital had a good hospice program.
Tim said he didn't know how much time he had. He knew the doctors could only guess at that because no one knows when the nodules will decide to start growing again.
Maybe the IL-2 had at least put the melanoma into a prolonged dormant phase, like it had with that other patient who was still stable more than a year after IL-2 treatment. Then, maybe not.
Tim said he liked Kevin. He said he thought this friendly young doctor, with the bright red hair, would have made a good country doctor, reassuring anxious families that everything was going to be just fine.
Then Tim thought about the specialty that Kevin had chosen for his career.
"It must be very hard," Tim said, as he slowly pushed a hunk of bacon into the yolk of the fried egg, "being in the type of work where all your patients die."
Tim went in for his third post-trial CAT scan Aug. 29. The nodule in his right lung had gotten bigger. The melanoma had started growing again.