DRUGS SHOW PROMISE FOR CANCER CURE.

Byline: Gina Kolata The New York Times

Within a year, if all goes well, the first cancer patient will be injected with two new drugs that can eradicate any type of cancer, with no obvious side effects and no drug resistance - in mice.

Some cancer researchers say the drugs are the most exciting treatment they have ever seen. But then they temper their enthusiasm with caution, noting that the history of cancer treatments is full of high expectations followed by dashed hopes when drugs with remarkable effects in animals are tested in humans.

Still, the National Cancer Institute has made the drugs their top priority, said Dr. Richard Klausner, the institute's director. He called them ``the single most exciting thing on the horizon'' for the treatment of cancer.

``I am putting nothing on higher priority than getting this into clinical trials,'' Klausner said. The mouse studies are ``remarkable and wonderful,'' he said, and ``very compelling.'' But he pointed out that the studies were in mice and so, in humans, he said he wanted to emphasize ``the ifs.''

The new drugs, angiostatin and endostatin, work by interfering with the blood supply tumors need. Given together, they make tumors disappear and not return.

Dr. James Pluda, who is directing the cancer institute's planned tests of the drugs in patients, said he and others at the institute were ``electrified'' when they heard the drug's discoverer deliver a lecture about the newest results. ``People were almost overwhelmed,'' Pluda said. ``The data were remarkable.''

Although the discovery of the drugs, and some of their effects, have been reported over the past few years, Pluda said that ``if people understood how many steps ahead'' the research was compared to what had been published, ``they'd be even more in awe.''

But Dr. Jerome Groopman, a cancer researcher at the Harvard Medical School, is wary. ``We are all driven by hope,'' Groopman said. ``But a sober scientist waits for the data.'' And until the drugs are given to humans the crucial data simply do not exist.

Good for mice

So far, the drugs are the only ones ever tested that can seemingly eradicate all tumors in mice, even gigantic ones, equivalent to a two-pound growth in a person. The best that other cancer drugs have done is slow the growth of these large tumors. Mice are the traditional test animals in cancer research.

But even the drugs' discoverer, Dr. Judah Folkman, a cancer researcher at Children's Hospital in Boston, is cautious about the drugs' promise. Until patients take them, he said, it is dangerous to make predictions. All he knows for sure is that ``if you have cancer and you are a mouse, we can take good care of you.''

Other scientists are not so restrained. ``Judah is going to cure cancer in two years,'' said Dr. James Watson, a Nobel laureate who directs the Cold Spring Harbor Laboratory, a cancer research center on Long Island. Watson said Folkman would be remembered along with scientists like Darwin as someone who permanently altered civilization.

The long trail to the discovery of the new drugs began more than 30 years ago, when Folkman became obsessed by what many saw as a quixotic notion: that cancers cannot grow beyond the size of a pinhead unless they have their own blood supply. If he could block a tumor's blood supply, he reasoned, the tumor should shrink to a minuscule size.

First breakthrough

The first major break in the efforts came a decade ago when Folkman and his collaborators found drugs that did what he envisioned. He called them anti-angiogenesis drugs because they stopped the process of developing new blood vessels, or angiogenesis. They slow tumor growth in animals but do not eradicate the tumors. Early results in patients indicate that the drugs may slow human cancers, too. Dozens of companies are now developing such drugs.

The results with these weaker drugs were ``a proof of principle,'' said Dr. Bart Chernow, a professor of medicine and dean for research and technology at the Johns Hopkins University School of Medicine. Chernow is a founder of Entremed, a company in Rockville, Md., that was formed to make and market angiostatin and endostatin as well as some of the weaker drugs that can slow cancer growth.

For the past four years, Folkman said, he and his colleagues have found that all tumors responded to the drugs in the same way. Even leukemia, a blood tumor, responds, he said, because it turns out that leukemia needs to form new blood vessels in the bone marrow to grow. Leukemia tumors grow on these blood vessels, ``like berries on a bush,'' Folkman said, shedding cancer cells into the blood.

But Folkman is the first to urge caution in leaping to conclusions about what might happen when patients try the drugs. ``Going from mice to people is a big jump, with lots of failures,'' he said.

Hopes were high for chemotherapy drugs that worked well in mice but turned out to be less successful in people. Therapies that used the immune system to rid the body of cancer also worked in mice but were disappointing when they were tried in people. Gene therapy treats mouse cancer, but has had limited success in people. From bitter experience, most cancer researchers have learned to be leery of what one called ``that four letter word'': cure.