NEW ORLEANS-A UC San Francisco study has found that an antibody that blocks the growth of blood vessels in tumor cells-essentially starving the tumor of oxygen and nutrients--can slow disease progression and shrink tumor size in patients with advanced colorectal cancer.
Emily Bergsland, MD, UCSF assistant clinical professor of medicine in the UCSF Comprehensive Cancer Center, presented the data at the 36th annual meeting of the American Society of Clinical Oncology (ASCO) here today (May 21).
The agent, developed by Genentech, Inc. is called recombinant humanized monoclonal antibody to vascular endothelial cell growth factor (rhuMAb-VEGF or anti-VEGF). It works by prohibiting the protein VEGF from activating endothelial cell growth. Endothelial cells make new blood vessels in a process called angiogenesis. Solid tumors cannot grow beyond the size of a pinhead without inducing the formation of new blood vessels to supply the nutritional needs of the tumor, according the National Cancer Institute.
"This is the first time that an agent specifically developed to block blood vessel growth has shown activity in a randomized clinical trial," Bergsland said. "These results are preliminary and need to be validated in larger clinical trials, but they do lend support to the idea that angiogenesis plays a critical role during tumor progression and represents a fundamentally new target for cancer treatment."
The Phase II trial enrolled 104 patients who were previously untreated for metastatic colon cancer. Metastasis is when the disease spreads to other organs in the body. Patients with metastatic colon cancer have a median survival rate of one year and their treatment options are fairly limited, Bergsland said. The patients were randomized into one of three arms: standard chemotherapy alone, chemotherapy in combination with a low dose of anti-VEGF at 5 mg/kg; or chemotherapy in combination with a high dose of anti-VEGF at 10 mg/kg. Patients were treated until they had progressive disease.
The study found a 40 percent response rate in patients receiving the low dose antibody in combination with chemotherapy. Response rate means their tumors reduced in size by 50 percent or more, Bergsland said. Twenty four percent of those enrolled in the high dose antibody combination arm responded to the treatment. And 17 percent of the patients on chemotherapy alone had shrinkage in tumors.
Time to disease progression, or how long it takes for the disease to worsen, was nine months in the low dose, combination arm and 7.2 months in the high dose combination arm. Patients receiving just chemotherapy had a time to disease progression of 5.2 months.
There was also a trend toward increased survival in patients taking the antibody. Median survival, or half of the patients, survived until 13.9 months in the chemotherapy only arm. For those on the high dose, median survival was 16.1 months. More than half of the patients are alive at 17.3 months in the low dose anti-VEGF combination arm.
"This study gives us a sense that we are heading in right direction and is an important step toward improving therapies available for cancer patients," Bergsland said.
Investigators are not sure why the lower dose of the anti-VEGF seems to produce better results in the patients, Bergsland said.
"While it is not clear why low-dose rhuMAb VEGF appears to be more active than the high dose, both arms of the study seemed to show increased benefit compared to the control," Bergsland said.
Other investigators are H. Hurwitz, Duke University, Durham, NC; Louis Fehrenbacher, Kaiser Permanente, Vallejo, CA; N.J Meropol, Fox Chase Cancer Center, Philadelphia, PA; William Novotny, Genentech Inc., South San Francisco, CA; Farooz Kabbinavar, University of California, Los Angeles; J. Gaudreault; G. Lieberman.
Genentech Inc. funded the study.