Oct. 14, 1998 Physicians at UCLA's Jonsson Cancer Center today (Oct. 13) launched a new experimental treatment for inoperable pancreatic cancer using a form of a virus that causes the common cold.
"Unfortunately, most patients with pancreatic cancer cannot be cured by surgery," said Dr. J. Randolph Hecht, lead investigator for the study at the Jonsson Cancer Center and an associate professor of medicine at the UCLA School of Medicine. "Usually, by the time the disease is detected, cancer cells have traveled beyond the pancreas or have spread too close to important blood vessels, making it impossible to safely remove all of the cancer."
Pancreatic cancer kills approximately 95% of the more than 25,000 Americans diagnosed each year with the disease, he said.
Rather than using surgery, the experimental treatment relies on a genetically engineered adenovirus -- called ONYX-015 -- that attacks only cells with alterations in, or an absence of, a gene called p53. (An adenovirus is a kind of virus that can cause the common cold.)
Hecht described the new strategy as one that strikes pancreatic cancer at its Achilles' heel.
"Alterations in or the absence of the p53 gene can leave cancer cells -- unlike normal cells -- vulnerable to attack by a virus engineered to destroy only cells which lack functional p53," he said.
In normal cells, p53 acts as a damage-control center that monitors cell growth and replication according to a specific plan encoded in the DNA. p53 also helps defend cells against infection by viruses.
When certain viruses infect normal cells, the viruses produce a kind of protein that binds to the p53 protein, thereby stifling p53's ability to function properly. With p53 out of the way and unable to protect the cells against the viruses, the viruses are free to hijack the cells' genetic machinery and transform the cells into factories that make more viruses, a process which destroys the normal cells.
ONYX-15 should not be able to replicate efficiently in normal cells that contain undamaged p53 genes, Hecht said.
"But cancer cells, which lack functional p53 genes, may not be able to protect themselves against the engineered adenovirus. The engineered virus can replicate in and destroy cancer cells in the same way a normal adenovirus can hijack a normal cell," he said.
"By injecting large quantities of the engineered adenovirus directly into pancreatic tumors, we are trying to turn the tables on the cancer cells," he said. "Viruses that infect cancer cells manipulate the central control mechanisms of the cells to produce more viruses. The process of making more viruses kills the cancer cells.
"We hope this study marks the beginning of a new era of targeted, more efficient, and more effective therapies that can be used against pancreatic cancer," he said.
The experimental treatment is administered through a series of internal injections into pancreatic tumors. To inject adenovirus into the tumors, physicians pass a needle through a hole in an endoscopic ultrasound device. The device, inserted through the mouth and guided down into the intestinal area, allows physicians to see the location of the cancer as they work.
"This approach is the first to combine advanced imaging technology with a viral treatment for pancreatic cancer that seeks out only the cancer cells," Hecht said. "Using an endoscopic ultrasound is more efficient because we can do many more injections in a single treatment, it's less expensive and it should be safer than conventional methods that use CT scanning."
Study participants will receive eight injections over an eight-week period. During the last four weeks, they also will receive gemcitabine, a chemotherapy drug approved by the FDA for use in treating pancreatic cancer. After eight weeks of adenovirus treatment, study participants will continue to receive gemcitabine for as long as their cancers respond to the drug.
"There is some preliminary information that the virus may make cancer cells more susceptible to conventional anti-cancer treatments such as chemotherapy," Hecht said.
The study is in the earliest stages of testing in humans. Physicians will use the results from this stage of the study to evaluate the safest and most effective dosage levels, and to identify potential side effects, which could include flu-like symptoms such as chills, fever or fatigue.
Onyx Pharmaceuticals in Richmond, Calif., developed the genetically engineered adenovirus.
Patients interested in participating in the study should call Mandy Parson, RN, at (310) 206-8161.
For more information on UCLA's Jonsson Cancer Center, its people and its resources, please visit our website at http://www.cancer.mednet.ucla.edu
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