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Reviewed By Brunilda Nazario, MD
Feb. 18, 2008 (San Francisco) -- A drug cocktail that starves tumors of their blood supply shows promise for the treatment of men with advanced prostate cancer.
A combination of Avastin and thalidomide -- both of which cut off the growth of new blood vessels that feed tumors, but in different ways -- appears to pack a more potent punch than Avastin alone, researchers report.
Avastin was the first of a new kind of cancer therapy that works by choking off the blood supply to a tumor, a process called anti-angiogenesis. It's already approved for use in fighting colon and lung cancer.
Avastin blocks a chemical signal called vascular endothelial growth factor, or VEGF. VEGF binds to certain cells to stimulate new blood vessel formation.
Many people have heard of thalidomide. Its use in treating sickness during pregnancy in the 1960s resulted in birth defects. The birth defects were caused because thalidomide changes the growth and development of new blood vessels, including those in developing babies.
But thalidomide also blocks the action of another chemical signal that spurs the growth of new blood vessels that feed tumors. This one's called fibroblast growth factor.
"We reasoned that combining two different anti-angiogenesis drugs that work by two different pathways to get to the same goal would result in improved antitumor activity," says researcher Yangmin Ning, MD, a researcher with the National Cancer Institute.
Combination Treatment for Prostate Cancer
Ning and colleagues studied 60 men with prostate cancer that had spread to other parts of the body. They were all given an anticancer cocktail that contained Avastin, thalidomide, and the chemotherapy drug Taxotere.
Taxotere, which is given with the steroid prednisone, is a standard treatment for men with advanced prostate cancer.
Results showed that 90% of men improved on the drug cocktail, as measured by a PSA drop of 50% or more.
PSA, or prostate-specific antigen, is a protein produced by cells in the prostate. High PSA levels can signal cancer; men with a faster PSA drop after treatment tend to have better outcomes. The National Cancer Institute says a reduction in PSA of 50% or more after treatment is a sign that the patient is responding to the treatment.
While the study did not directly compare the anti-angiogenesis cocktail with other drugs, Ning says typically only about 50% of men respond to the standard combination of Taxotere and prednisone.
Adding Avastin alone to Taxotere and prednisone raises the response rate to 60% to 70%, he tells WebMD.
"These data appear to support our hypothesis, which may lead to a novel strategy of improving Taxotere-based treatment of advanced prostate cancer," Ning says.
There were some serious side effects, including internal bleeding, clotting, and perforations (holes) in the colon, mainly due to Avastin. Three men had to drop out of the study due to Avastin-associated toxicities.
ASCO spokesman Howard M. Sandler, MD, a radiation oncologist at the University of Michigan, says the results are promising. He notes that results of a large clinical trial testing Avastin and Taxotere against Taxotere alone are due out next year.
"If a benefit is shown for adding Avastin, the standard of care for these patients will switch to Avastin plus Taxotere. This study is testing the next avenue of approach -- adding a third agent to that doublet," Sandler tells WebMD.
SOURCES: Genitourinary Cancers Symposium, San Francisco, Feb. 14-16, 2008. Yangmin Ning, MD, associate investigator, branch of medical oncology, National Cancer Institute, Boston. Howard M. Sandler, MD, spokesman, Genitourinary Cancers Symposium; department of radiation oncology, University of Michigan, Ann Arbor. Brian Rini, MD, Memorial Sloan-Kettering Cancer Institute, New York City.
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