BRISTOW
-- From her deathbed, Marina Symcox could hear laughter from
her daughter's birthday party downstairs.
Other days, she could hear the voices of ladies dropping off Miranda
after they picked her up from day care. Symcox had never met them, but
she thought of them as angels for being kind enough to help a dying
woman's family.
And through the upstairs window, she could hear children playing at the
school yard across the street. She wouldn't live long enough for her own
daughter to start kindergarten there or to see her sons grow up, she
thought.
"I will end, but they will go on without me," Symcox recalls telling
herself.
For eight months, she was in hospice and confined to her bed, expecting
to die from a rare cancer in her abdomen called gastrointestinal stromal
tumor.
"We really weren't expecting the next week," Symcox said. "We had come
to the end."
After three years of surgeries and several rounds of chemotherapy at
some of the nation's leading cancer centers, Symcox was waiting to die
and wondered why death was taking so long, she said.
She didn't face cancer stoically or philosophically.
"I was very bitter and angry," said Symcox, 45. "And I cried all the
time."
In the fall of 2000, her husband read on the Internet about a drug
trial that might help his wife. He managed to find a slot available for
her. And within days of her daughter's fifth birthday party, Symcox and
her husband, Keith, were flying to Portland, Ore., to enroll in the
program.
Symcox was so sick she could hardly stand. She wore maternity clothes
because the tumor had taken over her abdomen, making her look pregnant.
The experimental drug came with no guarantees. But no guarantee was
better than the other guarantees she had heard several times before --
that the chemotherapies she had tried definitely would not work.
So the Symcoxes figured that they'd try once more.
In all fairness, Symcox was too sick to qualify for the pharmaceutical
trial, and she knew it. So she lied. She told doctors that she still
drove a car and was much healthier than she appeared.
The doctors knew she was lying, Symcox said, and they knew she was
desperate.
On the Tuesday after they arrived at the Oregon Health and Science
University, Symcox's blood tests were not good enough for her to start
the therapy.
So she waited until Thursday for a retest. This time, her blood levels
were high enough for her to be approved.
But she had to wait until Monday to start, and her husband, who teaches
chemistry at the University of Tulsa, wondered whether his wife, also a
chemist, would survive the weekend.
She made it back to the clinic on Monday and was handed a bag of six
orange pills with a glass of water.
Past success
The pills Symcox was about to swallow already had been wildly
successful with a different kind of cancer -- chronic myeloid leukemia.
The medicine, called Gleevec, had a 99 percent remission rate with the
rare blood cancer.
The two types of cancer look different.
Chronic myeloid leukemia is caused by abnormal DNA in bone marrow,
while the gastrointestinal stromal tumor, usually called by its acronym
GIST, is a solid tumor that grows like mushrooms from the outer muscle
wall of the intestines.
But genetically, they are similar, said Dr. Charles Blanke, director of
the Solid Tumors Program at the Oregon Health and Science University
Cancer Institute.
That genetic similarity gave researchers hope that the same drug might
work for both cancers, Blanke said.
He was cautiously optimistic that Gleevec could work with GIST, Blanke
said, especially because "nothing else had even made a dent in this
disease."
Patients with advanced GIST usually died in 10 months, he said.
When a patient in Finland with GIST petitioned the drug company to
allow her to take Gleevec -- essentially a one-woman trial -- she had
amazing results, Blanke said.
Soon, an American and Finnish study began. It was supposed to have 36
patients, but was expanded to 150 just so that more people could have
access to the drug.
As news of its success spread, more GIST patients started clamoring for
the medicine. In late 2001, experts met in Washington, D.C., to approve
the fastest drug trial ever opened in the United States.
Soon, 746 patients in North America were taking the drug.
Patient No. 41 in Oregon was Symcox, who returned to her Bristow home a
few days later to continue the therapy.
Fixing what's broken
Gleevec is not chemotherapy, but a way of fixing the broken genes that
cause cancer cells to grow.
With GIST, a protein called C-KIT is like a light switch that is
clicked on to signal that cells should grow and divide. But it never
switches off.
Gleevec turns off that switch but does not affect normal cells.
Chemotherapy, however, poisons both good and bad cells, aiming to kill
more bad than good. That's why it is so toxic and makes patients so
sick, Blanke said.
In other words, Gleevec fixes what is broken. Research on Gleevec has
changed the way researchers are approaching other cancers and other
diseases, Blanke said.
"It taught us to think differently, to look specifically for the
mechanism that is driving the cells," Blanke said.
Melting away
Some of the Gleevec results were astounding. Some enormous tumors had
melted away in two weeks.
The results were quick and amazing for Symcox.
Two days after taking the pills, Symcox's belly became softer, she
said.
In 24 days, the tumor had shrunk to half its original size.
Within three months, Symcox could carry the laundry downstairs, and she
measured her progress by how many steps she could walk back up before
setting the basket down to rest.
Soon, her three children started treating her like a healthy mom again.
"Their clothes were on the floor again," she said.
A few of the patients in the GIST trial relapsed. But after three
years, half of the patients are alive and well, Blanke said.
Some have side effects of fluid collecting in the abdomen or bleeding
in the gut. But over time, the side effects improve, he said.
Scientists couldn't ask to work on a more exciting drug, Blanke said.
"If you're lucky, this is a once-in-a-lifetime phenomenon," Blanke
said.
The pill was so successful that Dr. Daniel Vasella, chairman and chief
executive officer of Novartis, the pharmaceutical company that makes
Gleevec, wrote a book titled "Magic Cancer Bullet: How a Tiny Orange
Pill Is Rewriting Medical History."
But he tempers his enthusiasm for Gleevec with the fact that it will
not work in all cancers and the reality that developing other
genetically targeted drugs is difficult.
"The problem," Vasella wrote, "is that so far in most cancers we simply
do not understand the critical abnormalities."
The map of the human genome will make the work easier by providing a
list of "parts" that make up the body, but scientists still will need to
know which gene is broken and how the abnormality causes a disease.
"We may find the answer to some cancers in a year or two; others may
take 20 or 30 years," Vasella wrote. "At least we know, thanks to
Gleevec, that we are on the right track. We know that we will reach
success in other forms of cancer; it's no longer a matter of 'if,' but
'when.' "
Supporting others
Symcox still has some "ifs" in her life.
Every three months, she has a CT scan to check for changes in her
abdomen.
The scans show numerous dark holes where the tumors once were in her
liver, but PET scans, which measure metabolic activity, show that the
GIST cells are dormant, she said.
She'll take Gleevec the rest of her life.
Even though Gleevec turns off the protein switch, the switch is still
around and can be clicked back on without Gleevec. Even after five
years, there is a chance of relapse.
That's why Blanke thinks of GIST as a chronic disease similar to
diabetes, which can be managed with regular medication, he said.
As Symcox continues the therapy to fight cancer, she and fellow
survivors have started a Web site -- www.gistsupport.org -- devoted to
fighting the disease. It includes a section where 280 patients share
notes by e-mail.
They help each other find the next drug trial if Gleevec isn't working,
and they help newly diagnosed patients find the help they need.
Especially with a rare disease like GIST, finding an expert, an
experimental drug and support can be difficult. Having family support is
also essential.
Symcox credits her husband for not giving up and for carrying her to
the trial when she could hardly move.
"I wonder," Symcox said, "how many people just go home and give up."
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