Researchers at UCLA's Jonsson Cancer Center today (May 30, 2001)
launched several studies of treatments for advanced breast and colorectal
cancers that attempt to starve tumors by cutting off the blood supply they
need to grow and flourish. The large studies are open at UCLA's Westwood
campus and at more than 60 affiliated cancer network oncology offices
throughout California and in Nevada and Montana.
Hundreds of patients are being sought to take part in three clinical trials
to study the experimental anti-VEGF antibody (Avastin) in combination with
chemotherapy on advanced breast and colorectal cancers. A product of South
San Francisco-based Genentech, the angiogenesis inhibitor is an
anti-vascular endothelial growth factor (anti-VEGF) antibody, meaning it
targets a protein that promotes new blood vessel formation, called
A tumor cannot grow bigger than a pinhead unless it establishes an
independent blood supply to provide the oxygen and nutrients it must have to
grow. Researchers hope that by stopping or cutting off the formation of a
new blood supply, they can starve and, hopefully, kill the cancer. In these
UCLA studies, the experimental antibody is teamed up with different
chemotherapy drugs. Researchers hope that the antibody will help the
chemotherapy work more effectively, and vice-versa, providing a synergistic
Dr. Fairooz Kabbinavar, a UCLA Jonsson Cancer Center scientist and physician
who has studied the anti-VEGF antibody in the lab and in patients for the
last nine years, heads up the three new clinical trials. Based on what he's
observed in the lab and seen in early patient studies, Kabbinavar is
optimistic about the effectiveness of the anti-VEGF antibody.
"This antibody seems to be the most active agent available to inhibit
angiogenesis, based on some of the laboratory and early clinical data,"
Kabbinavar said. "The antibody targets the dominant angiogenesis protein. In
the lab, we saw a definite synergistic effect when the antibody is combined
with chemotherapy. Results from early phase studies also appear to bear that
In addition to the Jonsson Cancer Center on UCLA's Westwood campus, the
antibody is available to patients in California community-based UCLA
research network oncology offices in Bakersfield, Fresno, Fullerton,
Inglewood, La Jolla, Lancaster, Long Beach, Monterey, Monterey Park,
Northridge, Oxnard, Pasadena, Pomona, Rancho Mirage, Redondo Beach, Santa
Barbara, Santa Cruz, Santa Maria, Santa Monica, Thousand Oaks, Valencia, and
Vista. In Nevada and Montana, the studies are open in offices in Las Vegas
and Great Falls, respectively.
Offering studies in UCLA-affiliated community oncology offices allows cancer
patients to receive state-of-the-art, experimental treatments closer to
home, said Dr. Dennis Slamon, director of Clinical and Translational
Research at UCLA's Jonsson Cancer Center.
Slamon, a renowned scientist and oncologist, is optimistic about the new
antibody. He called data from early laboratory and clinical studies "very
"The results were impressive," Slamon said. "This is a new and exciting
therapy and we're getting real results in early studies."
The experimental antibody has an advantage in that it requires
administration less often than other angiogenesis inhibitors, some of which
need to be given twice a week by intravenous infusion, requiring increased
patient visits. The anti-VEGF antibody is given only once every two to three
weeks, Slamon said.
Much of the early testing of the anti-VEGF antibody was done in UCLA Jonsson
Cancer Center laboratories and clinics. Two of the new studies focus on
colorectal cancer, while the third tests the antibody on breast cancer.
The following are summaries of the available studies:
* A Phase III study of the anti-VEGF antibody when combined with
(5-FU) and leucovorin, currently considered the "gold standard"
chemotherapy regimen for advanced colorectal cancer. About 900 people with
previously untreated advanced colorectal cancer are needed for the study,
which randomly assigns patients to one of three arms. One arm studies
Camptosar, 5-FU and leucovorin alone, while a second arm tests the three
chemotherapy drugs plus the anti-VEGF antibody. The third arm tests 5-FU and
leucovorin with the anti-VEGF antibody. In arms one and two, the
chemotherapy combination is given in repeating six-week cycles, with four
weeks of chemotherapy administered once a week, followed by two weeks of
rest. The antibody is given every two weeks. In the third arm, the
chemotherapy combination of 5-FU and leucovorin is administered in
eight-week cycles, with weekly chemotherapy for six weeks followed by two
weeks of rest. The antibody is given every two weeks. Patients receive
treatment for 96 weeks maximum or until their disease progresses. An early
phase study at UCLA that tested the anti-VEGF antibody combined with
chemotherapy for advanced colorectal cancer resulted in encouraging survival
data, which will be presented this week at the American Society of Clinical
Oncology meeting in San Francisco, Kabbinavar said.
* A phase II study of the anti-VEGF antibody with a different mix of
chemotherapy for patients with advanced colorectal cancer who can't tolerate
the "gold standard" combination because of their age or deteriorated health.
About 200 patients with previously untreated advanced colorectal cancer will
be randomly assigned to one of two arms this study, which tests the
chemotherapy agents 5-FU and leucovorin with and without the anti-VEGF
antibody. The chemotherapy is administered in eight-week cycles, with weekly
chemotherapy for six weeks followed by two weeks rest. The antibody is given
every two weeks. Patients receive treatment for 96 weeks maximum or until
their disease progresses.
* A Phase III study of the anti-VEGF antibody with the chemotherapy
pill Xeloda, an oral version of 5-FU, on patients with advanced breast
cancer. About 400 patients whose breast cancer progressed after either one
or two chemotherapy regimens will be randomly assigned to this two-arm
study, which tests Xeloda with and without the antibody. Patients take the
chemotherapy pill twice daily at home, and the antibody is given by
intravenous infusion every three weeks. Patients receive treatment for 96
weeks or until disease progression.
Early tests of the anti-VEGF antibody alone on patients with advanced breast
cancer resulted in "encouraging responses," Kabbinavar said.
"We're hopeful that the antibody will work even better when combined with
Dr. J. Randolph Hecht, a gastroenterologist and oncologist at UCLA's Jonsson
Cancer Center, serves as co-principal investigator for the colorectal
studies. The prognosis for patients with advanced colorectal cancer - cancer
that has spread to other organs - isn't good, Hecht said.
"The average life expectancy for metastatic colorectal cancer is just
slightly more than a year," Hecht said. "So there's a lot of room for
improvement. We were very encouraged by the survival rates in the early
studies, which were longer than normally expected. Now we have to do this
larger, randomized phase III study to confirm those results."
Dr. Linnea Chap, a researcher and medical oncologist specializing in ovarian
and breast cancers, serves as principal investigator for the breast cancer
Each year, about 180,000 American women are diagnosed with breast cancer.
More than 40,000 will die. About 135,000 Americans will be diagnosed with
colorectal cancer this year. Of those, more than 56,000 will die.
"These cancers are claiming far too many lives each day," Kabbinavar said.
"We need to find better ways to target these diseases."
For more information on the three studies, patients should call UCLA's
toll-free clinical trial hotline at 888-798-0719.