Drugs Aimed at Shutting Down Blood to Tumors Are Safe

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May 13, 2001 (San Francisco) -- More than two years ago, cancer researchers demonstrated that they could cure cancer in mice with new drugs that shut down a tumor's blood supply. This year, the preliminary studies of these drugs suggest that it will be some time before the drugs can make the same claim about cancer in humans. But on Sunday, researchers at the American Society of Clinical Oncologists meeting held here say they are nonetheless encouraged.

Tumors need oxygen to keep growing and blood carries oxygen to tumors, says John Mendelsohn, MD, president of the University of Texas M.D. Anderson Cancer Center in Houston. "No cell can grow unless it is oxygenated."

Thus, it is logical to think that pulling the plug on the blood supply could cause tumors to shrivel and die. Renowned cancer researcher Judah Folkman, MD, coined the term angiogenesis to describe the growth of blood vessels. When this growth is blocked he calls the process anti-angiogenesis.

One of the anti-angiogenesis drugs, called endostatin, was tested in 25 patients with various types of terminal cancer. Roy S. Herbst, MD, of the M.D. Anderson Cancer Center, says that none of the patients was cured by the drug but in two patients "tumors did shrink a bit." In one 58-year-old man with the deadly skin cancer called melanoma, "tumors initially grew by 100%, but then the tumors stopped growing and one tumor shrunk a bit."

These first studies in human are called phase I, or safety studies. The goal, says Herbst, is to determine if the drug is safe. "We did prove that the drug is safe."

In his study he also attempted to find out if the drug was effective at cutting off blood to the tumors. He used high-tech imaging technology, called positron emission tomography or PET scan, to track the tiny blood vessels that supply the tumors.

"By PET we demonstrated a statistically significant decrease in blood supply," says Herbst.

Endostatin targets endothelial cells, which are involved in the formation of blood vessels. Another anti-angiogenesis drug, code-named HuMV833, targets vascular endothelial growth factor known as VEGF, which is an enzyme that promotes the growth of new blood cells. A team of British researchers, led by Gordon C. Jayson, MD, PhD, studied this drug in 20 patients with advanced cancer.


Jayson tells WebMD that just like endostatin, this compound did not produce any significant results in the early study but again it was well tolerated. But Jayson says the study produced a more important finding: that each patient had a different "and individual reaction to the drug. Moreover, different tumors in the same patient reacted differently."

That means, says Jayson, that it may require several different types of anti-angiogenesis agents to completely shut down blood supply.

Michael Gordon, MD, associate professor at the Arizona Cancer Center in Phoenix, tells WebMD that he thinks that anti-angiogenesis will succeed "by using this cocktail approach." He says that the latest studies suggest that when given as a single drug "none of these agents has demonstrated enough activity to warrant a claim of a breakthrough therapy."

But he says that as cancer experts learn more about the biology of tumors they will be able to effectively mix the drugs together to mount a broad-based attack.

Gordon says, however, that such a cocktail is "a long way off."

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