New Trials For Anti-Cancer Drug Start

After decades of research, Andrus Professor of Pediatric Surgery M. Judah Folkman is one step closer to his research goal of attacking cancer by cutting off the flow of blood to tumors rather than attacking them directly.

This week, doctors will begin testing endostatin, a cancer-fighting drug developed from Folkman's research, on human beings for the first time.

Endostatin is the first of several anti-cancer drugs under evaluation which prevent angiogenesis, the growth of new blood vessels in the body. Doctors hope that, by stopping the growth of blood vessels around a cancerous tumor, the drug can shrink tumors and prevent the cancer from spreading.

Susan Craig, spokesperson for the Children's Hospital, Boston, where Folkman conducts his research, says that endostatin has been successful in studies on mice, reducing cancerous tumors to nearly microscopic size with no observable side effects.

Folkman has been working on restricting blood vessel growth, particularly near tumors, for over 30 years, according to Emery Professor of Organic Chemistry Elias J. Corey.

"The whole theory of angiogenesis inhibition was developed by Dr. Folkman," Craig said.

Folkman's research aims at preventing tumors from growing, rather than targeting them directly, as treatments like chemotherapy do, Corey said.

"If you block the supply of oxygen to tumor cells, then that's an approach to controlling tumors," Corey said. "It's a very interesting scientific hypothesis. [Folkman] has been working in a pioneering way to test that."

Although endostatin might prevent blood vessels in the body other than those around a tumor from forming, Corey said normal adult tissue can remain healthy without angiogenesis. Only tumors would be adversely affected, he said.

"The [new blood vessel] requirement for existing tissue is minimal," Corey said. "The requirement for rapidly-growing tissue is substantial."

The first endostatin testing on humans will be conducted by Dana-Farber/Partners CancerCare--a coalition of Massachusetts General Hospital, Brigham and Women's Hospital and the Dana-Farber Cancer Institute. Two other institutes, one in Houston and another in Wisconsin, will begin testing the drug later in the year.

Todd Ringler, a spokesperson for Dana-Farber/Partners CancerCare, said that the first phase of testing will look only for toxic side effects. Endostatin's effectiveness will be noted, but it will only be studied directly if the drug proves non-toxic.

Ringler said "hundreds" of applicants volunteered for testing. Only three were selected for the initial round of tests, although up to 27 more will be selected later. No control patients will be used, he added.

Ringler said the first phase of the study will take 9 to 12 months. Final, complete approval for human use will take years, he said.

Despite high public expectations, Ringler said that researchers are remaining cautious.

"This clinical trial is merely one of hundreds of clinical trials," Ringer said. "We want to keep expectations down."

Corey said historically, the odds are against endostatin succeeding.

"Only five to 10 percent of drugs survive human testing," Corey said. "Of those, one in five will turn out to be successful drugs."