Drug that cuts off tumor's blood supply extends lives of colorectal cancer
patients
03 Jun 2004



Promising results in Jonsson Cancer Center study

A drug designed to cut off a tumor's blood supply, when paired with a
chemotherapy combination, resulted in significant improvement in survival in
patients with metastatic colorectal cancer, the first time in decades that
survival times have been extended in patients with this devastating form of
advanced cancer.

The results of the study, done at UCLA's Jonsson Cancer Center and several other
sites nationwide, appear June 3, 2004 in the New England Journal of Medicine.

The study paired the angiogenesis inhibitor Avastin, approved by the U.S. Food
and Drug Administration in February for use in colorectal cancer, with
irinotecan, 5-fluorouracil and leucovorin. The combination therapy improved
median survival in patients by nearly five months, reducing risk of death by
more than 30 percent. It also improved response rates, duration of response and
progression-free survival times, said Dr. Fairooz Kabbinavar, a Jonsson Cancer
Center researcher and senior author of the study.

"To put this study in the right perspective, up until the year 2000, median
survival in patients with advanced colorectal cancer was about 12 months," said
Kabbinavar, an associate professor of hematology/oncology who has been working
with Avastin for the last 10 to 12 years, both in the lab and in the clinic. "In
just four short years, we're now looking at survivals in excess of two years.
We've come a long way. Avastin has not only changed the way we treat colorectal
cancer, but I believe it will become a part of cancer management for other
tumors such as lung, breast and pancreatic cancers."

A tumor cannot grow bigger than a pinhead unless it establishes an independent
blood supply through a process called angiogenesis. This process provides the
tumor with the oxygen and nutrients it needs to grow and spread. Researchers
have theorized that by stopping or cutting off the new blood supply, they can
starve and, hopefully, kill the cancer. Researchers had hoped that Avastin - a
monoclonal antibody that targets the Vascular Endothelial Growth Factor (VEGF),
a dominant protein that promotes growth of blood vessels - would help the
chemotherapy work more effectively, and vice-versa, providing what is called a
synergistic effect. Kabbinavar said the study proved there is such an effect.

"This is an important milestone in cancer management in general and in
colorectal cancer management in particular," Kabbinavar said. "Avastin is the
first angiogenesis inhibitor to be approved by the FDA, and we found it has
manageable toxicity. So patients not only live longer, but their quality of life
is also maintained."

In the study, 813 patients with previously untreated advanced colorectal cancer
were randomly assigned to two groups. In one group, 402 patients received
irinotecan, 5-fluorouracil and leucovorin plus Avastin. The other 411 patients
received the chemotherapy combination plus a placebo. The studied looked at
overall survival, progression-free survival, the response rate, duration of the
response, safety and quality of life.

Median survival, the time at which half of study patients are still alive, in
the group getting Avastin with chemotherapy was 20.3 months compared to 15.6
months in those getting chemotherapy and a placebo, reducing risk of death by 34
percent. Progression-free survival, the time before the cancer continues to grow
again, was10.6 months in the Avastin group compared to 6.2 months in the placebo
group. Response rates in the Avastin group were 44.8 percent, compared to 34.8
percent in the placebo group. Response duration in the Avastin group was 10.4
months, compared to 7.1 months the group getting the placebo with chemotherapy.

"The addition of (Avastin) to 5-fluorouracil-based combination chemotherapy
results in statistically significant and clinically meaningful improvement in
survival among patients with metastatic colorectal cancer," the study states.

After several disappointments with angiogenesis inhibitors, this study proves
that targeting a tumor's blood supply is a viable treatment option, Kabbinavar
said.

According to the American Cancer Society, colorectal cancer will strike more
than 146,000 Americans this year alone, killing about 56,730. Overall, colon
cancers are the third most common cancers in men and women, and the second
leading cause of cancer death in the United States.

UCLA's Jonsson Comprehensive Cancer Center is composed of more than 240 cancer
researchers and clinicians engaged in cancer research, prevention, detection,
control and education. The center, one of the nation's largest comprehensive
cancer centers, is dedicated to promoting cancer research and applying the
results to clinical situations. In 2003, the Jonsson Cancer Center was named the
best cancer center in the western United States by U.S. News & World Report, a
ranking it has held for four consecutive years.

-UCLA-

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

Contact: Kim Irwin
kirwin@...
310-206-2805 University of California - Los Angeles

http://www.medicalnewstoday.com/?newsid=9032

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