(Last year, five women with recurring cancer allowed Blade science writer Jenni Laidman and photographer Jetta Fraser to follow them through an experimental drug trial at the Medical College of Ohio. This is the second of a five-part series about that trial -- called "Working on a cure: Cancer on trial" -- begins a yearlong examination of cancer by The Blade.)
Pat Krzeminski whispers. She's not telling a secret, she's milking a moment. She's a master of using her voice this way.
“I am just dying to do something wild,'' she confides.
There's a pause. Then her words cascade, tumbling fast, like breathy rapids: “I want to get so drunk I don't even want to know who I am, and fall off the barstool, and just lay on the floor and say, ‘Where am I?'''
There's no whisper now. Everyone can hear her: “I don't even care if I wake up throwing up. I mean, I'm so used to throwing up.
“But you know what would happen? I'd beat the cancer, and die of alcohol poisoning.''
Pat cackles. Her listeners guffaw. For a moment, this group of cancer warriors in the Medical College of Ohio's Ruppert Center is hers.
Nested within this oft-expressed wish, with its mordant wisecrack at the end, is the theme of Pat's cancer treatment: If there's a strange twist in anybody's story, if something is about to go wrong, if the piano is falling toward an innocent pedestrian, she's that pedestrian.
This Murphy's Law view of fate is her refuge. She's not just a cancer patient. She's the special recipient of humorous calamities.
A shtick is born.
This is her second day of treatment with an experimental antibody known as H11. She vomited for hours after her first treatment. She was the only patient in the cancer drug trial to get sick.
By the end of 2001, 12 people with recurrent cancer will help drug developer Viventia Biotech Inc. of Toronto figure out how much of this new drug can be safely tolerated.
The people who play guinea pig in what is called a Phase I trial have no promise the treatment will do anything for them. The papers they signed commit them to a more altruistic goal: finding a dose that won't kill future, healthier, patients in whom researchers will seek a cure.
But in reality, altruism is secondary for the Phase I patients. It gains importance only if they think H11 is not helping them. Until then, every patient in this trial is hosting her own experiment.
Safe doses be damned, she is looking for a cure.
And for Pat, whose six years of cancer treatment has featured more vomiting than the average stomach-flu-swept preschool, there's no reason to get excited about a bit of nausea. Maybe it means her cells see something the vomitless patients are missing - that's the way she looks at it.
Her cancer cells, she hopes, are on notice.
The very word conjures visions of a compact, walled, enclosure: jail cells, monks' cells, the hexagonal cells of a honeycomb.
In all of these enclosures, cell doors seem almost beside the point. But cells without doors aren't worth watching. Doors are the thing if you're a cell.
Biological cells have doors as well, and everything depends on what enters these portals. What passes depends on the door itself.
These doors, through which so much important commerce routes, are made of protein.
Proteins aren't just hamburger. Forget the cow on hoof.
Instead, think of complex, foldable, twistable whatnots, marvelous toys with near magic abilities. In one form, proteins twist into chunnels for cellular vehicles. In another shape, they are the mail, messages carried from cell to cell. Then again, proteins stretch out and link to form such connective tissue as collagen. As insulin, proteins keep blood sugar levels regulated. Proteins even fold into antibodies such as the H11 dripping into Pat's veins.
Genes get all the attention, and the recipes they contain are invaluable to the cellular choreography. But genes without proteins are like bosses without secretaries.
Nothing gets done. Nobody answers the phone.
Genes write the recipes for proteins. Proteins do everything else. Figuring them out is the next challenge of biology. Armies of scientists study how they bend and twist into sheaths, spirals, and corkscrews. Their folding, their embraces, are more than curiosities.
Proteins are life's purposeful origami.
A protein spanning a cell's membrane has the dual function of being both the lock and the door. Messenger proteins can sidle up to the door, but unless they bear the proper combination of felicitous shape and electrical charge, entrance is refused.
When the messenger fits snugly in a protein door, it doesn't always enter. Sometimes its presence alone sends a signal to the cell's insides. Other times, the messenger simply blocks the passage from other visitors.
Even cancer cells - mutant, hobbled, maladaptive - have membranes studded with protein portals.
While good cells are citizens extraordinaire, the cancer cell is a rebel. Good cells do nothing without the permission of their cellular community. A petri dish growing normal cells will stop once the dish surface is covered with cells, says William Maltese, chairman of the Biochemistry and Molecular Biology Department at MCO.
“They will realize they're in contact with other cells, and the signals from touching those other cells will turn switches so they stop dividing,'' he says.
A dish with cancer cells is soon a pile of cancer cells. The cells crowd. They climb. They pile up like train wrecks, like soccer melees. They riot.
Still, the hope is, even a cancer cell will stop growing if the right message makes it through.
The question is, is H11 that message?
Pat is sure H11 signaled something, or she wouldn't have been so sick last night. Despite her optimism, she's a little nervous at being the only one nauseated. She tells the nurses. They take it in stride. She tells the other patients. Mary Griffith noticed a metallic taste after treatment, and felt a little lightheaded, but she wasn't vomiting like Pat.
Pat turns it into a joke. She's hiding her nerves.
But still, she manages to pass word to Sarah Lyons. She wants Sarah to know she was sick.
Sarah Lyons is the woman who interviewed Pat when she signed up for the H11 trial, and she's the one who explained to each patient what to expect. Her official title is protocol coordinator at MCO's Cancer Institute, but she's more like the Trial Mom.
Dr. Iman Mohamed, a breast cancer specialist, is officially the top MCO investigator on the H11 trial. And Dr. Donald Braun, the head of the MCO Cancer Institute, is important enough to serve as a scientific adviser to Viventia.
But for patients, there's only one face to this research, and it's Sarah Lyons'.
Slender, with large dark eyes and a spiky pixie haircut, Sarah's good looks would fit right in on the set of Friends. While she can rapid-fire the medical acronyms with which nurses communicate, she drops the eruption of alphabet soup when she talks to patients.
She's smooth - a ballerina in a tornado.
When patients are scared, they come to Sarah. When they're unhappy with rules, they're at her door. When they're jockeying for position, it's Sarah they try to play.
When they're desperate and terrified and looking for a miracle, they'll find her home number and call her there.
“This is last-stop shopping,'' Sarah says. “If this doesn't work, some of them are probably going to die very soon.'' Her voice falters as she says these last words. She blinks back tears.
She understands the desperation that drives patients. Her mother has advanced breast cancer. It's not going to get better.
Sarah reassures Pat easily.
“Nausea and vomiting are not side effects we're worried about,'' she says. Blood clotting is the No. 1 concern, and Pat's reaction has nothing to do with that.
OK, Pat says. What's a little more vomit? In the last six years, Pat's lost most of her rectum, more than half of her vagina, her ovaries and uterus. What's a meal or two compared to all that?
“If this is how you have to figure it out, then this is how you have to figure it out. I can deal with it,'' she tells Sarah.
Sarah, in the meantime, is twirling through her day.
Besides the H11 patients just outside her office, Sarah's e-mailbox overflows. Her phone rings. A dozen times a week or more she hears from frantic people all over the country, all over the world. Each wants a shot at the antibody trial.
It's a desperate parade.
A couple from Virginia call. The husband has terminal lung cancer. His doctors hold out no hope. But the wife sees H11 as the miracle she's looking for. She'll bring her husband to Toledo if only Sarah gives the word.
There's a man with prostate cancer in Florida who is ready to fly to Toledo on Sarah's OK.
One week a man calls from Singapore.
“I don't know how he got my number. He called me. It was like 3 o'clock in the morning his time. His mother was just diagnosed. He said, ‘I don't care about the costs,' but she has central nervous system metastases.'' The study design excludes anyone with cancer in the brain and/or spinal cord.
The study design also excludes the Florida prostate patient - he's not sick enough, and the Virginia lung-cancer patient, he's too sick, sicker than even Cissi Jackson.
Cissi Jackson sits in the same recliner every day of her antibody treatment. She looks frail. But she's talking miracles.
“You have control over your body,'' she says. “What the mind can do is amazing.''
“I'm so excited. I feel so thrilled. I'm a survivor.''
No one else believes that.
Even her oncologist, Dr. Mohamed, did not expect Cissi to survive for long, the doctor says later.
By the second week of the trial, Cissi's declarations have gone from optimistic to extraordinary. Looking up from her Danielle Steele novel, she proclaims: “The medicine is working.
“I'm gaining weight, too, with this treatment. It means I'm not feeding the cancer, I'm feeding myself.''
She wears a blue denim shirt with flowers embroidered on the pockets. Her earrings are tiny scissors. A seamstress and gardener, she goes home each day to design majorette uniforms and wedding dresses. It's early March, yet she's already thinking of the wisteria she wants to plant in her yard.
Cissi's cancer is Stage 4. In other words, it metastasized to sites distant from the original tumor.
The record of her medical treatment since her first cancer diagnosis in 1992 is baffling. To hear Cissi and Dave, her husband, tell it, her medical care has been inconsistent at best.
Although Cissi rarely is fazed by the things that have happened, Dave has grown critical of a medical establishment that seemed sometimes haphazard with his wife's care.
Cissi discovered breast cancer nine years ago when a large lump developed at her right nipple. A mammogram revealed cancer, and a mastectomy followed. Already the tumor had spread. More than half of the lymph nodes removed during surgery were positive for cancer. Once cancer cells are in the lymphatic system, they can travel anywhere in the body.
Chemotherapy and radiation followed the surgery. One year after her initial diagnosis, a blood test showed no sign of cancer, Cissi says. That was the last time she saw a doctor for breast disease. He never suggested another visit and Cissi never insisted.
“They didn't ask me, and I forgot about it,'' Cissi says.
Instead of worrying about the cancer, she focused on what she accomplished during treatment.
“I had no trouble,'' she says. “This was nothing. I made 23 bridesmaids and wedding gowns that year.''
By 1996, the cancer was back. Cissi found a lump on her left breast. Tests revealed it was too late for another mastectomy. The cancer was in her sternum.
Thus began a continual regimen of chemotherapy.
Frustrated by the lack of progress in his wife's condition, Dave went to the Internet. He came up with the name “Herceptin''- an antibody, as is H11.
“We went in and told the doctor about Herceptin,'' Dave says.
Herceptin is an important drug for the 25 percent to 30 percent of all breast cancer patients whose tumor cells bear too much of a protein called HER2.
In normal cells, chemicals called growth factors can bind to the HER2 protein and signal the cell to grow and divide.
But in some cancer, the cells produce extra HER2. As the protein accumulates, it no longer waits for an external signal. Instead, the clusters somehow short circuit, sending growth signals on their own. Cancer proliferation follows.
When a patient takes Herceptin, the antibodies attach to the HER2 proteins. It's believed that Herceptin blocks the HER2 growth signal. Herceptin may also recruit other immune cells to come in and kill the cancer cell.
For six months, Herceptin worked for Cissi. Then her cancer grew accustomed to the treatment. It evolved a way around it. The cancer was growing again.
Dave went back to the Internet.
Somewhere around this time, Cissi's previous oncologist gave up.
“He couldn't do anymore,'' Cissi says, “but he didn't put it in those words. He said, ‘It will be sad not seeing you around anymore.'''
The doctor's coy revelation of her prognosis clearly irks her. It's a rare show of dissatisfaction for a patient who normally effervesces.
The doctor's mindset, more than any treatment decision, finally got to Cissi.
“I'd have to go in and cheer him up. I thought, well, they've given up. I don't care if they've given up. I haven't given up.''
Dave's research uncovered the H11 trial under way at MCO.
“You can't sit back, because these doctors seem to be doing all the sitting back,'' Dave says.
Cissi came to MCO, and Dr. Mohamed became her new oncologist. Dave considers the doctor an answer to prayers.
By this time, Cissi was so far gone, Dr. Mohamed talked to the couple about hospice. But the doctor also saw opportunities for treatment. For one thing, Cissi never received a key drug in the care of breast cancers like hers, a formulation called Arimidex.
Arimidex is hormone therapy. One of the things keeping Cissi's cancer cells growing is the hormone estrogen. Although the 61-year-old is post-menopausal, her body converts chemicals produced by the adrenal glands into estrogen.
Arimidex disrupts that process.
“It is amazing this woman has not seen this medication when she's been seen (by oncologists) for so many years,'' Dr Mohamed says.
Cissi seems untouched by previous medical errors.
“They're people too. They make mistakes.''
Still, Dr. Mohamed holds out little hope for Cissi's survival, even with Arimidex and H11.
“She was homebound, on oxygen, thin. She couldn't do anything,'' the doctor says. Hard lumps of tumor cover Cissi's back, scalp, and belly. Cissi complains that one at her throat chokes her.
She has a condition called “carcinoma en cuirasse,'' Dr. Mohamed explains. It's a French term. Cuirasse means “shield.” The cancer wraps Cissi's chest wall tightly. She fights it for every breath.
By the second week of antibody treatment, the H11 women are an ad hoc support group. One afternoon they bring food for a potluck. Usha Mohan makes chicken curry, Cissi a fruit pizza, Pat Krzeminski brings cookies.
The women discuss family members and nail polish colors. A new store in Perrysburg draws raves. They kid with the nurses. Carol Albright, a nurse in the infusion center, laughs at Pat's latest hair color. It's an unearthly shade. Recent chemo keeps the color from adhering properly.
“Honest to God, you're a women of all hair colors.''
Then she looks at the message shaved into Pat's short-short hair: “No. 1 Dr. Fanning.''
“She's such a brown-nose,'' Carol says.
“All we need is a keg of beer, and we would be all right,'' Pat says of the daily gathering.
Another nurse, Dana Pyles, is pregnant with twins. She turns in profile and shows off her pregnancy - barely a blip on her slim form.
“My head is bigger than that!” Pat shouts.
They befriend other patients. A Bowling Green State University professor becomes an honorary member of the H11 posse when he comes in for regular treatment. Pat wears size 10 bright red cowboy boots to tease the boot-wearing prof.
Pat keeps everyone apprised of her weekly nausea.
“I threw up all over myself at 75 mph. There were trucks all around. I couldn't get over,'' she says. It happened on the second Monday of her treatment. Monday sickness becomes so routine patients speculate that their bodies object to the antibodies after a weekend off.
But no one is complaining.
“Actually, this is the simplest thing I ever had,'' Mary Griffith says. “I told Don (her husband) I hope that doesn't mean no pain, no gain.''
But there is little encouraging news as Pat ends her second week of experimental treatment. On the morning of March 8, Sarah Lyons hears that the first person to enroll in the H11 trial has died.
It's the second death among H11 patients. Both women were in the lowest dose group. Both started with very advanced cancer. Neither death is related to the treatment.
An hour or so after she hears of the death, Sarah gets word that the U.S. Food and Drug Administration is halting enrollment to the MCO cancer trial.
Pat and the others can complete their therapy, but no new patients will be admitted to the trial. The risks appear too high.
The FDA is worried about blood coagulation deaths in experimental animals. They want to make sure patients aren't at risk.
Tomorrow: Red Man Syndrome strikes.
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