Good News For GI Cancer Patients
Pioneering better methods to treat gastrointestinal cancers that cannot be treated with surgery has also increased knowledge of genetics, leading to more effective treatment of the cancers.
by Phil Davis
When surgery failed to eliminate the cancer in Judy Che's stomach and abdomen, her doctors began telling her to make the most out of the remaining months of her life. The prognosis: "Hopeless," recalls her husband, Carl, minister of the Orange County Chinese Christian Church.
Her doctors advised her to take a long vacation with Carl and her two recently married daughters-before the cancer ravaged her body.
But Che, a 58-year-old nurse, was not ready to give up. The couple hurled themselves into learning about experimental treatment options for the cancer-a search that ended at the USC/Norris Comprehensive Cancer Center and Hospital with Heinz-Josef Lenz, M.D.
Lenz, assistant professor of medicine and scientific
director of cancer genetics at USC/Norris, is pioneering better methods
to treat gastrointestinal cancers that cannot be treated with surgery.
In Che's case, Lenz began a chemotherapy regimen that combined the anti-cancer drug cisplatin with bryostatin, a natural agent found in sea urchins that makes the body more receptive to chemotherapy. Within six weeks after she enrolled in the clinical trial, Che's tumor and the cancer cells in the fluid of her abdominal cavity vanished.
"A miracle," Carl Che beams. Judy smiles.
Lenz, too, is ecstatic. Che's cancer remission is more than just good news for her family-it is an important step forward in applying an increased understanding of genetics to the treatment of all cancers.
"We now have patients flying in from all over the country for this protocol," Lenz says. "This is a very exciting time. We have the information, the know-how and the patients to make this work."
People suffering from gastrointestinal cancers-gastric, pancreatic and colorectal-could use a little good news. Che's doctors were pessimistic with good reason. Statistics said that she was most likely going to become one of the estimated 13,700 Americans who will die from stomach cancer in 1998. The odds of her survival were less than 20 percent.
The bad news is an estimated 183,200 Americans like Che will be diagnosed with some form of gastrointestinal cancer this year, according to that American Cancer Society. More than half that number will die.
The good news is increased knowledge of genetics is leading to more effective treatment of the cancers and an end to the one-size-fits-all approach to cancer treatment. In the not-too-distant future patients will receive cancer treatments tailored to their unique genetic makeup.
The key to more effective cancer treatment lies in how the body responds to certain drugs and therapies. In Che's case, the bryostatin appears to have pushed the right internal buttons in her body to increase the effectiveness of the chemotherapy. Recent tests have detected no cancer.
For Will Richardson Jr., a 75-year-old retired investment analyst, a drug that showed promise in the treatment of breast cancer is working extremely well in the treatment of his colon cancer.
"The colon tumor disappeared and the liver lesions melted away," Lenz says. "It's an incredible response to this new drug."
Lenz and his USC colleagues have obtained approval from the National
Institutes of Health to run a clinical trial to treat colon cancer with
the new drug-xeloda-after the discovery that breast and colon cancers both
have high levels of a similar enzyme. To scientists, the enzyme indicates
that both cancers might be susceptible to the same drug.
Such markers can also identify cancers that are not susceptible to certain treatments. Peter Danenberg, Ph.D., USC professor of biochemistry and molecular biology, and his team recently defined two tumor markers that indicate which colorectal cancer patients will not respond to chemotherapy. Clinical trials are underway to determine if the discovery can be used to better plan treatment of colorectal cancer.
Until recently, 5-flourouracil (5-FU), was the only chemotherapy known to be effective in treating colorectal tumors. Still, only about 20 percent of the patients respond to the drug-leaving the remaining 80 percent to undergo an expensive and unpleasant treatment that was not helping them. Since there is no way to tell who will or won't respond to the drug, everyone gets the treatment-a broad approach to fighting the disease born of necessity.
"It's standard therapy," Danenberg says. "All drugs, especially with colorectal cancer, have very low response rates-20 to 25 percent. So that means three out of four patients get this treatment but don't benefit from it. But there's no choice. They still have to go through it."
But two tumor markers with tongue-twisting names-thymidylate synthease (TS) and dihydropyrimidine dehydrogenase (DPD)-have been found to be strong indicators of which patients will not respond to the 5-FU chemotherapy. Clinical trials are currently underway to exploit this theory-and could lead to sparing up to 90 percent of all colorectal cancer patients unnecessary chemotherapy, Danenberg says.
"We hope in the future to avoid a fruitless treatment in a number of patients," Danenberg explains. "And we will be able to increase the overall response rate by designing treatments specific to how a patient is mostly like to respond. If this works, we will almost double the response rate to cancer therapies by presorting the patients."
Communication and close cooperation between USC's scientists and their colleagues around the world is crucial in order to bring research out of the laboratory and into a clinical setting. Lenz's research is being expanded to other universities in an effort to gather sufficient data to ensure the treatments are effective and bring them into the medical mainstream.
For Judy Che, knowing she is helping to advance medical science boosts her spirit almost as much as the good news that her cancer is on the run.
"I hope to help myself and also to benefit others," she says.
Will Richardson agrees. But he also knew that cutting edge medicine was his best chance for survival.
"I'm in the hands of the scientific director of genetics. He's a whiz," Richardson says of Lenz. "It's been a very enjoyable experience. I hope everyone has a similar experience."