From University of California - Los Angeles
Study pairs two targeted therapies A new, early phase study at UCLA's Jonsson Cancer Center for the first time pairs two molecularly targeted drugs as a one-two punch to fight metastatic breast cancer. The drugs attack only the cancerous cells, and leave the healthy cells unharmed.
Jonsson Cancer Center researchers are seeking volunteers with untreated, HER-2/neu positive advanced breast cancer to participate in the research, which does not use chemotherapy or other conventional treatments. The study combines the monoclonal antibody Herceptin with the experimental angiogenesis inhibitor Avastin, which current studies indicate may extend the lives of patients with advanced colorectal cancer.
"Other research on advanced cancers using these drugs has shown potential survival benefit for subjects, so we are now conducting research to test the drugs in combination against advanced breast cancer," said Dr. Mark Pegram, director of the Women's Cancer Program Area at UCLA's Jonsson Cancer Center and principal investigator for the study. "Now we're comfortable enough to give them in combination without any chemotherapy."
Pegram said the combination of targeted therapies may attack the cancer in different ways, fighting the disease on two fronts. Women with HER-2/neu positive breast cancer have cells with too many growth factor receptors, causing the cells to grow out of control, similar to a car with a stuck accelerator. Herceptin, approved in 1998 by the U.S. Food and Drug Administration for use against advanced breast cancer, acts like a brake, blanketing the growth factor receptors and blocking the signals telling the cells to grow.
Women with HER-2/neu positive breast cancer also have increased angiogenesis, a process by which tumors develop an independent blood supply to provide the nourishment that cancer needs to grow and spread. Avastin blocks the formation of this blood supply, cutting off the oxygen and nutrients to the tumor and, it is hoped, starving the cancer to death.
"If we can hit both the growth factor receptor and stop the tumor cells from growing and, at same time, prevent the blood supply from forming to the tumor, we should expect to see great efficacy," Pegram said. "We have data from the lab to show that this is true. That's why we're so anxious to test this combination of drugs in human subjects." Avastin made national headlines earlier this month after positive results in advanced colorectal cancer patients were announced at the American Society of Clinical Oncology meeting in Chicago. In combination with chemotherapy, Avastin extended survival in patients with advanced colorectal cancer by about 30 percent. Herceptin in combination with chemotherapy has also been shown to increase survival in patients with advanced breast cancer by about 30 percent.
Because these drugs target only the cancer cells and tumor blood vessel cells and leave the healthy cells alone, Pegram expects the combination to have far fewer side effects than chemotherapy. Chemotherapy acts like a non-specific bomb in the body, killing all the fast growing cells and causing such side effects as hair loss, nausea and low white and red blood cell counts.
Study volunteers will receive Herceptin by infusion once a week, and Avastin by infusion every two weeks. The study is a Phase I/II clinical trial, meaning researchers are seeking to determine a safe dose level as well as measure the effectiveness of the two drugs in combination.
This is the first time these two drugs are being studied together. UCLA's Jonsson Cancer Center is the only site in the world offering this study, Pegram said.
Interested volunteers should call 310-825-8375 to see if they qualify to participate in the study.
For more information about UCLA's Jonsson Cancer Center, its people and resources, visit www.cancer.mednet.ucla.edu/.