MONDAY, April 8, 2002 (HealthDayNews) -- Scientists have preliminary evidence that a genetically engineered version of a common
cold virus may treat colon cancer and other gastrointestinal cancers
that have spread to the liver.
In early experiments, patients treated with the virus lived twice as
long -- one year -- as they were expected to survive without the treatment. The findings were presented yesterday at the Society of Cardiovascular & Interventional Radiology's annual meeting in Baltimore.
Though the therapy involved alterations to the gene, it was not gene therapy in the purest sense of the term, experts say.
"It's not genetically modified in a therapeutic sense," says Dr.
Thomas Weber, director of colorectal cancer screening and the cancer
family registry at Montefiore Medical Center in New York City. "There's
no extra gene put into the virus to deliver chemotherapy. It's not a
traditional vector for delivery, but it is engineered to be less
virulent as a virus, and that's to facilitate tolerance to it and reduce
the side effects of taking it."
Colon cancer claims the lives of about 55,000 Americans every year,
making it the nation's leading cancer killer after tobacco-related
malignancies. Colorectal cancer, which is cancer of the colon lining,
often spreads to the liver and, once this has happened, there are few
treatments available.
"It's certainly a very important area," Weber says. "Most of the
deaths [from colorectal cancer] are the result of metastatic disease to
the liver, so there really is a paucity of effective therapies for
metastatic cancer to the liver."
This trial, which took place at three sites around the United States
was a Phase I trial, meaning it was designed to see whether the treatment was safe and well tolerated by patients. The survival results were a surprising side effect.
"Because it was a Phase I-type study, survival statistics are not
strictly and scientifically valid," says lead author Dr. DanielY. Sze, an assistant professor of cardiovascular and interventional radiology at Stanford University Medical Center. "We were looking for hints and trends that would help us decide whether or not to pursue a Phase II study."
In the trial, 35 people with gastrointestinal cancer, most of which originated in the colon, were given the virus therapy. Of those, 28 got it in high doses, while the other seven received "dose escalation" therapy.
"Dose escalation trials are particularly useful when we have little
understanding of what doses could be dangerous. Therefore, we started at a very low dose with the first patient, and inched our way up with each successive patient," Sze says.
Almost all the patients had already undergone chemotherapy and all had an abnormality in the p53 gene. The virus was designed to attack only cells with this abnormality, which is present in about half to two-thirds of cancers. Normal p53 genes act to find and kill early cancers; those with the abnormality are particularly susceptible to
malignancies.
"Theoretically, the virus could be used to treat any tumor that had
mutant p53, whether it had spread or not," Sze says.
In the trial, the virus was well tolerated among the patients. Most
patients felt like they had a mild flu for about a week, and were not as ill as they had felt after chemotherapy, Sze says. The median survival time for the 28 patients who received the highest dose was one year.
Using the virus as a standard treatment is years away, but Sze says
the early signs are hopeful.
"New therapies such as this must first become third- or second-line
therapies when there are approved chemotherapies available," Sze says.
"Eventually, engineered medicines and agents such as this will likely
replace the poisons we use today, but it won't happen overnight."
A Phase II trial of the virus is expected to start this year, and will treat cancer patients with both the virus and chemotherapy to try to confirm the beneficial effects of the virus.
What To Do
For more information on the latest research, visit the National Colorectal Cancer Research
Alliance.
