Experimental Drugs Give Cancer Patients Last Hope for Survival : Medicine: An ailing railroad worker opts to negotiate the uncertain voyage through the unpredictable maze of clinical trials.

At first, Al Kekich wouldn’t admit that he was sick.

He was strong, with a wiry endurance from years as a railroad man. And he had never had a serious illness or been a patient in a hospital. As one doctor observed, “He’s made of sturdy stuff.”

Kekich always demanded much of his body and it never let him down. He thrived in the long, unforgiving hours of his railroad work, laboring to raise three children in a blue-collar neighborhood of Baltimore.

Whispers of mortality 12 years ago prompted Kekich to quit drinking and to cut down on cigarettes. He never felt better.

But in the spring of 1990, at age 48, something was wrong.

It started as a diarrhea, mild enough to ignore at first.

Kekich didn’t talk about it, not even with his wife, Antoinette. He assumed his body would right itself. It always had before.

The problem persisted.

“It became evident to me . . . when I was doing the laundry,” his wife recalled. “He was showing blood in the stool.”

Antoinette Kekich, a telephone operator at Baltimore’s St. Agnes Hospital, called doctors and arranged her husband’s first journey into the world of medical science.

It was not a pleasant trip.

X-rays and other tests detected a tumor in his colon. It probably was benign, he was told, and an operation would correct it.

When he awoke from the surgery, however, Kekich learned that the tumor was malignant and had spread to his liver.

His doctors made no effort to soften the blow.

“You’ve got the big one,” the doctor said. This stage of colon cancer is usually fatal.

Antoinette Kekich remembers the doctor’s words vividly.

“The shock was quite. . . . “ She stops and shakes her head. “I was a little blinded by it all.”

Thus, Kekich joined the millions of Americans with a fatal cancer and needing nothing less than a medical miracle to survive.

Dr. Ross C. Donehower devotes his career to searching for that miracle.

Donehower and other doctors at the Johns Hopkins University Oncology Center direct clinical trials of experimental cancer drugs. There are more than 1,400 such trials now under way at more than 100 U.S. hospitals, most under the direction of the National Cancer Institute.

Thousands of people like Al Kekich enter the trials looking for one last chance at beating cancer. Most already have received the standard treatment and had little or no improvement.

In return for a long-shot chance at survival, the patients offer up their bodies for science. They let the doctors pump into their veins experimental compounds that may attack their cancer and almost certainly will make them sick.

Chemicals in the trials have already undergone an elaborate program of laboratory testing. But their ultimate value can only be determined in humans.

How the patients react tells researchers whether a chemical has good anti-cancer activity. The tests can also tell if the drugs are dangerously toxic.

“For diseases like cancer, there isn’t really any substitute for clinical trials,” said Donehower.

Doctors directing cancer clinical trials find that it is a job that challenges the mind--and breaks the heart.

“Most of my patients are destined to die,” said Donehower. “What you hope to do is to allow them to live as much of their lives symptom-free or as close as to symptom-free as possible. . . . You get disavowed of the notion that you’ll save a lot of lives.”

Oncologists try to insulate themselves, but some deaths are like sandpaper on the soul.

“There are certain patients who, no matter how you try to resist it. . . .” said Donehower. He looks away and starts again, “You have to ration your emotional energy. You can’t give everything to every patient. Then you would burn up.”

Al Kekich wasn’t going to let the cancer get him without a fight.

After his first surgery, Kekich remembers that his doctor at St. Agnes explained “kind of bleakly” that they could try conventional chemotherapy.

“It would have been stupid to not try,” he said. “I agreed to aggressive treatment.”

Kekich was put on chemotherapy with a drug called 5-fluorouracil. At first there was nausea and diarrhea, but Kekich shook it off.

Four months after the surgery, a computer-assisted X-ray--CAT scan--found more tumors, this time in a lung. Once again, the doctors called for surgery.

“As a kid, if we heard they were cutting on someone, then it was beyond hope,” said Kekich. “That was real bad news.”

Surgeons took out the lung tumors and four months later Kekich started a second round of chemotherapy.

Tests in the fall of 1990 showed the tumors were still growing and Kekich’s doctor recommended radiation therapy. He endured 30 treatments, with few side effects, and growth of the cancers appeared to halt.

On Jan. 18, 1991, Kekich went back to work. He had endured 18 months of surgery, chemotherapy and radiation.

“The doctor wrote a letter that said the cancer was in remission,” he recalls. “I thought, that’s great, if true.”

Kekich dropped back into his old routine on the railroad, often working through the night hauling freight from Baltimore to Richmond or to Cumberland and back. He felt well.

But in the fall, a follow-up X-ray found cancer in both lungs.

His doctor suggested that Kekich try experimental drugs at Hopkins. The odds were poor, they both knew.

“What could happen, the doctor said, is that I’d help someone else by testing these drugs,” recalls Kekich. “At least, that’s the way I read it.”

He thought about it awhile and then decided: “What the heck--I’ll go give it a shot.”

The Hopkins Oncology Center is a bustling front line in the war on cancer.

Patients jam the spartan waiting room. Some bear the unmistakable stamps of cancer therapy--scarfs covering bald heads, faces drawn, bodies emaciated or crippled. Most sit quietly, looking up hopefully each time a nurse walks by or calls a name.

Kekich, by now a veteran of such waiting rooms, is called and he meets Donehower. They are a study in contrasts. The patient, compact and wiry, with a wisp of mustache. The doctor, in his white clinical coat, stands well over 6feet.

Donehower was impressed with Kekich’s condition. Patients with colon cancer that has spread to other organs generally die within eight months of diagnosis. But here was Kekich, almost two years past his diagnosis, and still able to work. The doctor recognized him as an ideal drug trials candidate.

“The idea that cancer drugs are tested in patients who are severely compromised by their disease is generally not accurate any more,” said Donehower.

Instead, researchers prefer patients who have received all of the standard therapy and, except for the cancer, are generally healthy. Patients like Kekich.

Donehower’s job now was to help Kekich understand his options.

“Usually, there are three ways we can go,” said the doctor. “We have to find the patient’s level of comfort.”

Option one is to stop trying to conquer the disease and treat only the symptoms. This is a surrender-all-hope choice.

A second option would be a drug that has had some success, but is still experimental and of uncertain effectiveness.

“The chances that these drugs will work are smaller than I would like, but they still aren’t zero,” Donehower tells his patients. “The chances might be 5% to 10%.”

The third option is an experimental drug now in early clinical trials. Some have been tested on a number of patients, but researchers are still seeking the tolerable dose, one that kills the cancer, but not the patient.

Donehower tells his patients, “We’ll continue the therapy as long as it seems to be working. As soon as it appears not to be working or if the side effects become too unpleasant, then we’ll stop.”

Even if insurance pays most of the cost, as it does with Kekich, choosing to enter the drug trials requires a huge sacrifice, said Donehower. A patient gives up many of what may already be a precious few days left of active life. And the effects of the drugs can be devastating.

Added to that is the hospital aggravation: blood tests, X-rays, appointments, hours in waiting rooms.

Kekich chose to accept the experimental new therapy, and Donehower suggested a drug that was being tested on 30 other people at Hopkins in a phase one trial, a drug called CPT11.

The drug, an extract from an Indian plant called camptothescin, is one of a rare few compounds discovered by U.S. scientists in a worldwide search across forests, jungles and prairies for natural substances that might have some anti-cancer action.

Donehower started Kekich on the highest dose of CPT11 ever tried at Hopkins. He thought that if Kekich could withstand the side effects, a series of powerful CPT11 doses seemed his best chance.

For his first dose, Kekich checked into Hopkins overnight. Donehower wanted him to have close medical supervision in case of a dangerous toxic reaction.

CPT11 made Kekich sicker than the earlier chemo and radiation therapies. There was nausea and diarrhea. The drug left him with a bone-deep exhaustion.

But once again Kekich bounced back. He went home from the hospital after one day and back to work later in the week.

He put his name back on the list of “extra” workers on the railroad crew, which meant he could be called at any time and be required to report with just two hours’ notice.

It was exhausting work even without the chemotherapy, and Kekich cherished his single day off every week. But now, with the clinical trials, he lost that too.

Kekich showed up at Hopkins every Tuesday morning wearing a Baltimore Orioles cap, carrying a newspaper folded to the sports section. Many other patients came in their Sunday best, but it was Kekich’s day off and he wasn’t about to dress up. Some days, he defiantly wore a sleeveless T-shirt, leaving his muscular arms and shoulders bare.

On appointments between the chemo doses, the hospital did blood work and Donehower would interview and examine Kekich.

Cancer is usually the last thing doctor and patient talk about. Baseball is the first. Both are dedicated Orioles fans and the game was their common language.

When the doctor asked how he felt, Kekich always replied, “Oh, I’m OK.”

“He’s a tough guy who never complains,” Donehower told a visitor. Then he asks specific questions.

Kekich admits that he had diarrhea, nausea and couldn’t eat. It lasted for days, would stop, and then suddenly return, he said. Some times he was awakened by cramps. He sometimes felt “lazyfied” with no energy.

Was there difficulty in swallowing? No. Soreness in the mouth or gums? No. Difficulty in urination? No.

Donehower takes notes and then prescribes more anti-nausea and cramp medicine.

“Believe me, without that, it would be much worse,” he said. “This is not therapy for the fainthearted.”

Kekich takes the prescription form and they say their goodbys.

Every third Tuesday during the trial, Kekich received the experimental drug CPT11. First he had a thorough medical examination, more blood work and perhaps an X-ray.

Then he was led into a room with a hospital bed. He got comfortable, lying back in his Orioles cap. A nurse turned a valve, sending fluid from four bags overhead flowing through tubes and into an artery in Kekich’s shoulder.

First there were four different types of anti-nausea drugs. Kekich talked and read the paper and kept checking the fluid level. He was anxious to get through and go home.

“When will you start with the good stuff?” he asked a nurse, referring to the CPT11.

“It’s here now,” she said.

A few minutes later, Kekich said, “Oh, boy, I can feel it. I’m beginning to get a little woozy.”

Visitors are shown out the door.

Five times Kekich went through a CPT11 cycle. The first two were rugged. Then it got easier; the last was the easiest of all.

In July, Donehower told Kekich that he “faced an important decision.”

A scan was scheduled for the following Tuesday to see if CPT11 was attacking the cancer. If the tumors were not smaller, the therapy would be stopped, Donehower said.

Kekich nodded.

“Nobody ever promised me anything,” he said. “Either it worked, or it didn’t work.”

There was to be no miracle for Al Kekich.

In the CAT scan, ghostly images of death in lungs and liver were unchanged. Somehow, the tumors defiantly thrived against the toxic shock of CPT11. There was no doubt now about the disease outcome.

Donehower quickly assured Kekich that there is other therapy, though not as promising as CPT11.

“It’s not three strikes yet,” said Kekich hopefully.

“No,” said the doctor. “It’s not three strikes yet.”

But both knew that it was in the late innings of Kekich’s ballgame. They didn’t talk about it.

Kekich decided to wait two weeks, until after vacation, to decide what next to do. Donehower agreed.

The vacation had been dreamed of for months. Two weeks in Ocean City, Md. A family gathering with all three children, including the son from California. All six grandchildren. Fishing, long hours on the beach. Something to think about besides work and the damnable cancer.

There was the unspoken acknowledgment that it could be the last such summer.

Donehower grinned broadly when he spotted Kekich back at Hopkins. Kekich had a deep tan and there was a swagger of health about him. Somehow, his body had thrown off the residue of CPT11 in the sun of Ocean City.

Kekich talked of catching large, fat flounder and cooking them for the family. There had been glorious days, he said.

Now it was a time for decision, the doctor prompted.

“I think I’m going to take a break,” said Kekich. He was feeling well and after more than two years of surgery, chemotherapy and radiation, he wanted some time away from medicine.

“I have no doubt at all that I would be doing the same thing,” said Donehower.

Kekich, the doctor said later, will die of his disease. But there was no sense in trying any new treatment, not while he felt well. Everything reasonable had been done.

There’ll probably never be a paragraph or even a footnote in medical history about Kekich. His experience is but one data point in a mass of statistics about how CPT11 acts against cancer.

Donehower called Kekich “a special kind of individual” who had the nerve to try the drug at a high dose. “We got a lot of information from him about the maximum tolerated dose,” said the doctor.

And for some patients in the future, that high dose might make a critical difference. For them, CPT11 might work. Though they’ll never know his name, there someday could be hundreds, perhaps thousands, who live on because Al Kekich helped show the way.

That’s the future. For now, a doctor sought the right words to say to a disappointed patient.

“You can look back and know that you did everything that could be done,” Donehower told Kekich.

Doctor and patient smiled at each other and Kekich promised to check with the physician in a few weeks. There’d be another CAT scan in two months. But right now, “I want to drive somewhere by myself,” Kekich said.

He walked to the parking lot, stood beside his beloved maroon pickup and fidgeted. Kekich was impatient to get going and salvage what was left of his day off.

The healthy may squander time, but every minute was precious now to Kekich.

He was glad that he tried the experimental drug. “I had to know I was doing everything I could,” he said.

Did he expect now to beat the cancer? It was a question never asked of the doctor or discussed with his wife.

“Probably not,” said Kekich. “I think it will kill me.”

But he wanted no sympathy. There could be worse problems, he said. And nobody has forever.

“You know, I see kids in the hospital with cancer. They’ve got dreams too,” said Kekich. “The main thing is to find some inner peace about it. I am now more peaceful than ever before.”

He started his pickup, waved and drove away.