Treatment Shows Promise in Shrinking Colon Tumors

May 21, 2000
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Doctors at UCSF Medical Center have 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.

Dr. Emily Bergsland, an oncologist at the UCSF Helen Diller Family Comprehensive Cancer Center, presented the research results at the annual meeting of the American Society of Clinical Oncology on 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 involved 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 groups: 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 group responded to the treatment. And 17 percent of the patients on chemotherapy alone had shrinkage in tumors.

Time to disease progression, or the time it takes for the disease to worsen, was nine months in the low dose group and about seven months in the high dose group. Patients receiving just chemotherapy had a time to disease progression of about five months.

There was also a trend toward increased survival in patients taking the antibody. Median survival, or half of the patients, survived for about 14 months in the chemotherapy-only group. For those in the high dose group median survival was about 16 months. More than half of the patients in the low dose group were alive at about 17 months.

Investigators are not sure why the lower dose of the anti-VEGF seems to produce better results, 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.