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Steve Garrick, 47, of Crescent, holds up a Gleevec pill. He is surviving a rare cancer known as gastrointestinal stromal tumor, or GIST, thanks to the breakthrough drug.
Pete Erickson / The Bulletin
A path to survival
New medication gives patients with a rare form of cancer hope for the future
By Markian Hawryluk / The Bulletin
Published: September 18. 2008 4:00AM PSTSteve Garrick, a 47-year-old mill worker from Crescent, had no telltale pains or lumps. There was no routine screening exam or blood test that identified a problem. Early in 2007, he was just worn out.
“I started feeling extremely exhausted. I could not walk. I could not do my job very well,” he recalls. “It was just draining.”
Garrick went to see his doctor in March, who discovered he was “four pints of blood low,” and he underwent a transfusion. As his doctors started looking for the cause of his blood loss, Garrick underwent diagnostic test after diagnostic test: nuclear imaging, swallowing a tiny pill camera, and finally in May, a CT scan that found a bleeding tumor in the lower part of his small intestine.
He was rushed into surgery, where doctors cut away 6 inches of intestines on each side of the tumor. A few hours later, they told Garrick his tumor was a rare form of cancer known as a gastrointestinal stromal tumor.
Garrick had never heard of that type of cancer, known by the acronym GIST. He also didn’t know at the time that only a few years earlier, his prognosis would have been quite dire. For a significant number of cases, surgical removal of the tumor represents only a temporary solution. And when the cancer spreads, surgery is often no longer an option.
But an innovative cancer pill called Gleevec has given patients like Garrick new hope. The pill has extended the average survival past surgery from about 18 months to five years or longer. Despite the fact that the pill won’t work for everybody and won’t work forever, it’s a success story that’s being held up as the paradigm for cancer research.
Yet, without a determined group of patients and advocates pushing for a cure, Gleevec might never have happened. Now GIST patients are pushing for greater awareness of their condition in hopes of raising more funds for research and finding a true cure.
Second chances
After his surgery, Garrick was told about Gleevec but was hesitant to start taking medications. Confident that his surgeon had removed all of the cancer, he opted to wait and see. “I had it in my mind that it was gone,” he said.
He felt better for the first two months after surgery, but then fell back into a feeling of exhaustion. In December, he underwent another CT scan, which showed the cancer had returned. This time, Garrick opted for Gleevec.
“It’s been working pretty darn good ever since,” he said.
So much so that he has been able to go back to work and live a normal life, burdened by only a few manageable side effects: nausea, fatigue and some gastric distress.
GIST is a cancer of the connective tissues of the body, unlike more common cancers that tend to grow out of the lining cells of the affected organs. GISTs form in the gastrointestinal tract, often growing quite large before any symptoms appear. Symptoms are often vague: a feeling of fullness, abdominal discomfort or, as with Garrick, unexplained blood loss. Most GISTs are found accidentally; a mass appears on a CT scan, or a colonoscopy reveals the tumor.
In the past, these tumors were extremely difficult to treat, especially if surgery wasn’t an effective option. They do not respond to chemotherapy or radiation. In many cases, the cancer would return after surgery, often spreading to other organs where it could no longer be safely removed.
But about 10 years ago, a group of Japanese researchers showed that GIST was caused by a mutated enzyme. “It was mutated to be overly active,” said Dr. Michael Heinrich, a GIST specialist and medical school professor at Oregon Health & Science University. “This was a broken thermostat. It was always on, and the cells were always being stimulated to grow and divide.”
At the time of the discovery, Gleevec was being tested in the United States for the treatment of chronic myeloid leukemia, or CML. Researchers at OHSU and Harvard Medical School knew Gleevec targeted enzymes similar to the ones implicated in GIST. After test tube studies showed Gleevec could indeed kill GIST cells, they started testing the treatment in live patients.
“When it finally advanced to clinical studies, the results were amazing,” Heinrich said. “The first 10 people who were treated, they all responded dramatically within days or weeks.”
Some of the patients were in hospice at the time but were released to go back home. Others who couldn’t get out of bed because of their pain before the treatment went back to work or resumed golfing.
“It was really miraculous in its effect,” he said. “In someone with advanced disease that treats with Gleevec, the average survival is five years, which is three to four years longer than earlier in the decade. And some of the people who went on Gleevec eight years ago are still doing well.”
And unlike chemotherapy, which can have debilitating side effects that erode the quality of life, Gleevec is generally very well tolerated. Gleevec patients, for the most part, have good quality of life.
“You could be in a room with somebody on Gleevec and never know it,” Heinrich said.
Gleevec is now being used as a way of preventing the cancer from returning after surgery. Even when patients appear cancer-free after removal of the tumor, they may take Gleevec for years afterward to reduce the risk of a relapse.
Further research
For many GIST patients, Gleevec represents only a temporary stay. Over time, many tumors will develop a resistance to Gleevec and resume growing. In 2006, a second drug, Sutent, was approved for GIST patients. Most patients will be treated first with surgery, then Gleevec. If and when Gleevec fails, they are prescribed Sutent.
And seeing the success of Gleevec — with more than $2.6 billion in annual sales — there are a number of new drugs in the pipeline. Researchers believe GIST patients may one day take a long succession of drugs, moving to the next as their cancer develops a resistance. Or patients might be given a cocktail of drugs, much as is now done with HIV therapy, in hopes of preventing recurrence.
“There’s no evidence that these drugs cure the cancer, but they significantly have changed the outlook in some patients from well under a year or even six months (to live) to potentially many, many years,” said Dr. Stephen Kornfeld, the Bend Memorial Clinic oncologist who is treating Garrick.
Oncologists believe that cancer could one day be converted into a chronic disease that cannot be cured but can be managed for a lifetime.
“We don’t cure diabetes, high-blood pressure or cholesterol. We treat them chronically and convert them to chronic diseases,” Heinrich said. “That’s where we need to go for cancer.”
There’s hope those other drugs might work for people for whom Gleevec did not. There are a number of variations within GIST, and not everybody responds the same to the available treatments. The pediatric form of GIST, which represents a small minority of cases, is one of the forms that does not respond to Gleevec.
Targeted therapies
The Gleevec model way well represent the future of cancer research. The breakthrough came from the scientific study of the disease, finding the enzyme responsible, then matching up a drug that could target that enzyme. Such targeted therapies work best in cancers such as GIST or CML in which a single protein abnormality can be implicated. More common cancers, such as breast or colon cancers, are the result of multiple protein abnormalities. Still, there’s great hope that targeted therapies could provide the answer.
“The hope is that we are on the threshold in which those kinds of advances begin to happen in the more common cancers,” Kornfeld said. “This is the way oncology is heading, more toward rational therapeutic development of targeted therapies.”
Such drugs, however, are extremely expensive, about $4,000 to $5,000 a month. Some insurance companies are now starting to balk at covering the high cost of this treatment for the remainder of the patient’s life. Some have created a separate tier of coverage for Gleevec and Sutent, covering only 80 percent of the drugs’ costs; a 20 percent co-payment, however, can leave patients spending $1,000 per month.
“If you have a drug that really works, that patient may be on that drug for three or four years,” Kornfeld says. “You’re going to keep on taking it and it adds up. I see this playing out every day in my office.”
While financial concerns will be an issue, patients are more concerned about how long the two available drugs will continue to keep their cancer at bay.
“Until they can find a drug that for sure either stops the tumor growth or makes it go away, the fear in the community is that the Gleevec and the Sutent is going to be outrun by the cancer,” says Ginny Asp, a GIST survivor from Sunriver. “So the research money to go further is imperative. There are some really hellacious stories out there.”
Asp, 65, was diagnosed with GIST last year and had surgery to remove the tumor. She is not taking Gleevec but undergoes semi-annual CT scans to see whether the cancer — which she refers to as “old skanky” — returns. More than a year after surgery, she remains cancer-free.
Asp and Garrick are now part of an effort to raise more research funds. They will hold a fundraising walk in La Pine Sept. 27 to benefit the GIST Cancer Research Fund (see “If you go” on Page F1). The fund was created by Tania Stutman, a GIST patient from Rockland County, N.Y.
Stutman was diagnosed in 1998, well before any treatments other than surgery were available. Despite being told she had less than a year to live after her surgery, she survived three years before being accepted into one of the first larger clinical trials of Gleevec. The cancer has spread to her liver, but Gleevec helped her survive 10 years past surgery.
Last year alone, the research fund donated $700,000 directly to GIST researchers. The fund is run by volunteers and none of the funds donated to the cause are used for overhead.
“It’s very easy for everyone to jump on the wagon and help support the known cancers,” Stutman says. “People are not aware that very rare forms of cancers do exist and people are dying from it.”
Knowledge about GIST is, for the most part, limited to the GIST community, she says.
“It a very hard place to be, because it’s a rare form of cancer that’s never addressed in public,” she says. “You cannot bring it to the public eye. It’s very sad.”
Heinrich says that without the funding provided by such patient groups, Gleevec might not have been developed.
“The GIST groups have raised the money for us. They’ve donated a lot of money to us and to other major GIST centers, and a lot of our best technology that we used to study the problem, we could never have raised the money from a grant,” he says. “I’ve written grants and the first line is ‘GIST is very rare,’ and you know that nothing good is going to follow because they don’t think it’s important enough.”
Heinrich says Novartis, the pharmaceutical company that manufacturers Gleevec, nearly pulled out of the development of the drug numerous times when company officials doubted the limited market for Gleevec could recoup the development costs. It’s now the company’s second-most-profitable drug.
Garrick hopes the walk this weekend will not only raise funds but help raise awareness about the condition.
“A lot of people have never heard of it and they can’t really relate to it,” he says. “Breast cancer, everybody is aware of that. But with GIST, it’s like, ‘Is that really important?’ Well, it is.”
Markian Hawryluk can be reached at 541-617-7814 or mhawryluk@bendbulletin.com.
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