For Immediate Use June 24, 1999
Kambra McConnel ([email protected]) (310) 206-3769
Kim Irwin ([email protected]) (310) 206-2805
UNIQUE STUDY OF GENETIC TREATMENT FOR OVARIAN CANCER SHOWS POSITIVE FINDINGS AT UCLA'S JONSSON CANCER CENTER
An experimental genetic treatment for ovarian cancer has yielded promising results for some women whose disease failed to respond to conventional treatments, according to a preliminary study at UCLA's Jonsson Cancer Center.
Physicians today begin seeking volunteers recently diagnosed with ovarian cancer to participate in a new study of the genetic treatment, which targets alterations in a gene called p53. Defects in this gene are linked to approximately 57 percent of ovarian cancers.
"For a first-phase clinical study, the results were really provocative. We didn't expect to see such positive findings in patients with advanced disease that had not responded to surgery or chemotherapy," said Dr. Mark Pegram, co-investigator for the study at UCLA's Jonsson Cancer Center and an assistant professor at the UCLA School of Medicine.
About one-third of the p53 genetic treatment study participants experienced a 50 percent or greater reduction in tumor size, or saw levels of a cancer marker called CA-125 decrease. Elevated levels of CA-125, a protein produced by ovarian cancer cells, can indicate that ovarian cancer is present in the body. Decreased levels of CA-125 suggest cancer is responding to treatment.
Ovarian cancer is the leading cause of death among all gynecologic cancers. According to the National Cancer Institute, 26,800 American women will be diagnosed with the disease in 1999. Of those, 14,200 women will die.
"We're optimistic about the next phase of p53 studies because ovarian cancer is ideally suited for regional therapy," Pegram said. "The cancer remains in the abdominal and pelvic cavities throughout most of its lifetime, so it logically follows that we may effectively attack the cancer by periodically infusing doses of the gene therapy directly into those areas.
"I call this the 'new oncology,' " he added. "Cancer is caused by mutations in the genes of normal cells. So if you want to successfully treat cancers, you should develop drugs specifically to fight the mutations involved."
Unlike traditional chemotherapy that kills both cancer cells and healthy cells, the experimental treatment relies on repairing defective p53 genes. Targeting cancer cells without harming healthy cells helps patients avoid chemotherapy-induced side effects such as hair loss, severe nausea and weakened immune systems.
In all normal cells, p53 acts as a damage-control center that monitors cell growth and replication according to a specific plan encoded in the DNA. However, damaged p53 genes cannot properly control cell growth or replication. The unrestricted cell proliferation that results from a lack of functional p53 genes can cause cancer.
UCLA cancer physicians use a type of adenovirus - engineered so it cannot cause infections - to deliver normal p53 genes to ovarian cancer cells. (An adenovirus is a kind of virus that causes the common cold.) The adenovirus enters the cells and is expected to restore normal p53 function, thereby either repairing or killing cancer cells.
Possible immune reactions to the adenovirus may include flu-like symptoms, fever, fatigue or stomach upset. However, these conditions can be controlled with medication such as acetaminophen (Tylenol), Pegram said.
Through a randomized selection process, participants in the newly opened study will receive chemotherapy alone or in combination with genetic treatment. The worldwide study will further assess the experimental treatment's safety and effectiveness as compared to conventional therapies.
In the first phase of clinical study, UCLA physicians found that the experimental treatment is safe and that it successfully delivers normal p53 genes to cancer cells. They also observed early evidence of the treatment's effectiveness.
For phase I study participant Patricia McCallick, the experimental genetic treatment has proven successful so far. CT scans in May revealed no evidence of cancer in her body.
McCallick, 59, originally was diagnosed with advanced ovarian cancer in November 1997. Surgery and aggressive chemotherapy failed to kill the cancer, so her physician recommended that she consider participating in the p53 study.
"I wasn't scared when the chemotherapy and surgery didn't work because it's not in my nature to be scared. Instead, my first thought was, 'What do we do now?' This study seemed to be my only recourse and I was delighted to have something else to try," McCallick said.
McCallick also received moderate doses of chemotherapy as a supplement to some of the experimental genetic treatment. Preliminary laboratory research indicates that the combination of p53 genetic treatment and certain chemotherapy drugs attack cancer cells more forcefully than either approach used alone, Pegram said.
A resident of Ventura since 1994, McCallick teaches fifth grade at a school in North Hollywood. She enjoys golf, sailing and spending time with her three grown children and one grandchild.
McCallick is very encouraged by her progress in the study, which she completed in February.
"I'm hoping that I won't need anymore treatments, but I'd definitely go into another clinical trial if necessary," she said. "I think it's so important for doctors to continue doing research through clinical trials and for cancer patients to participate in them, because that's how future cancer treatments get developed."
For more information, patients interested in participating in the p53 genetic treatment study should call (310) 825-8375.
-UCLA-
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