Drug that cuts off a tumor's blood supply shows promising results when paired with chemotherapy

December 28, 2002

An experimental drug designed to cut off a tumor's blood supply showed promising results in patients with advanced colorectal cancer when paired with standard chemotherapy, according to a UCLA Jonsson Cancer Center study published in the Jan. 1 issue of the Journal of Clinical Oncology.

The results of this and subsequent studies of the experimental drug Avastin could change the way oncologists treat patients with this devastating form of cancer, said Dr. Fairooz Kabbinavar, a Jonsson Cancer Center researcher and first author of the peer-reviewed journal article. The combination of Avastin and chemotherapy proved superior to chemotherapy alone in treating advanced colorectal cancer, Kabbinavar said.

"This is a first-ever randomized trial of a potent anti-angiogenic agent, comparing chemotherapy alone to chemotherapy and Avastin in patients with advanced colorectal cancer," said Kabbinavar, an associate professor of hematology/oncology at UCLA who has studied this drug in the lab and in patients for the last decade. "This study could give us a less toxic and a more effective weapon in our growing arsenal of cancer therapies."

A tumor cannot grow bigger than a pinhead unless it establishes an independent blood supply through a process called angiogenesis to provide itself with oxygen and nutrients. Researchers theorize that by stopping or cutting off the new blood supply, they can starve and, they hope, kill the cancer.

In this study by UCLA's Jonsson Cancer Center researchers and scientists at four other sites nationwide, the angiogenesis inhibitor Avastin was given with the chemotherapy drugs fluorouracil (5-FU) and leucovorin in a two-pronged attack. Researchers hoped that Avastin -- a monoclonal antibody that targets the Vascular Endothelial Growth Factor, a protein that promotes growth of blood vessels -- would help the chemotherapy work more effectively, and vice-versa, providing a synergistic effect.

Results from laboratory and early-phase studies confirm that the drugs help each other to work better, Kabbinavar said.

Patients in the Phase II study detailed in the journal article who received Avastin with chemotherapy had better response rates and median survival times than did patients who were given chemotherapy alone. In addition, those who received the combination also had a longer time before their cancer progressed and had lower levels of a colon cancer marker in their blood than did patients who received chemotherapy alone, Kabbinavar said.

"The patients who got Avastin and chemotherapy did better in all the parameters we use to measure efficacy," Kabbinavar said. "This is a promising study that provided strong enough results to move on to a large Phase III study involving 1,000 patients."

The Phase III study, also conducted at UCLA's Jonsson Cancer Center and other sites nationwide, was recently completed. Results are expected sometime next year and should provide researchers with a more definitive answer, Kabbinavar said.

"Our hope and our expectation is that the data will hold true in the larger study as well," Kabbinavar said. "This drug combination may prove to be an important new option for patients with newly diagnosed metastatic colorectal cancer."

Avastin and other angiogenesis inhibitors attack cancer differently than do conventional therapies. Chemotherapy works like a non-specific bomb inside the body, attacking all fast-growing cells and often resulting in debilitating side effects such as nausea, hair loss and a dangerous drop in white and red blood cell counts. Angiogenesis inhibitors fight cancer by preventing or cutting off the blood supply that tumors must have to thrive and spread.

In this Phase II study, 104 patients with untreated, advanced colorectal cancer were given Avastin and chemotherapy or chemotherapy alone. Median survival was increased from about 13 months in patients who received chemotherapy alone to about 21.5 months in patients who were given Avastin and chemotherapy.

Median time to progression, or the time until the cancer grows again after treatment, was increased from 5.2 months in the chemotherapy only group to 9 months in the group receiving Avastin and chemotherapy.

Response rates also were better, with 40 percent of the group getting the combination therapy showing a significant response to the drug, versus 17 percent who responded to the chemotherapy alone.

And patients who received the combination therapy had a 54 percent lower risk of disease progression than did those on chemotherapy alone.

"These preliminary results suggest that Avastin, in combination with 5-FU and leucovorin, increases response rate, prolongs time to progression and prolongs survival," the article states. "These data support further evaluation of the efficacy and safety of Avastin."

Colorectal cancer will strike about 148,000 Americans next year alone, according to the American Cancer Society. More than 56,600 people will die from the disease.

Advanced colorectal cancer is incurable, Kabbinavar said. Most patients die within a year, so it's vital to find new and better ways to treat this disease.

"It's important for patients with advanced cancers to talk to their oncologists to see if there are any clinical trials available," he said. "They need to be proactive and seek out all options."
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For more information on Jonsson Cancer Center studies, call 888-798-0719.

For more information on the Jonsson Cancer Center, visit our Web site at www.cancer.mednet.ucla.edu/.

University of California - Los Angeles

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