Human trials planned for 2 drugs that eradicate cancer in lab mice Combination works against any tumor, without side effects

May 03, 1998|By NEW YORK TIMES NEWS SERVICE

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 people.

Still, the National Cancer Institute has made the drugs their top priority, said Dr. Richard Klausner, the director. Klausner 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," he said. The mouse studies are "remarkable and wonderful," he said, "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 from what had been published, "they'd be even more in awe."

But Dr. Jerome Groopman, a cancer researcher at the Harvard Medical School, was 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, he said, the crucial data simply do not exist.

So far, the drugs are the only ones tested seem to eradicate all tumors in mice, even huge ones equivalent to a 2-pound growth in a human. 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, Folkman said, 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 such scientists as Charles 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.

The first major break in the efforts came a decade ago when Folkman and his collaborators found drugs that did so.

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 DTC research and technology at the Johns Hopkins University School of Medicine. Chernow is a founder of Entremed, a company in Rockville that was formed to make and market angiostatin and endostatin, as well as some of the weaker drugs that can slow cancer growth.

But the real breakthrough -- and the two new drugs -- came from Folkman's efforts to understand a peculiar phenomenon that has been known to cancer surgeons for 100 years: sometimes a patient will have a single tumor, with no evidence whatsoever of metastases, the satellite cancers that can pepper a patient's body.

A doctor will remove the tumor and all will seem fine. But then, a few months later, a whole series of metastases will appear, grow and kill the patient.

In 1989, Folkman proposed a reason: a tumor could be making both stimulaters and inhibitors of blood vessel growth. The inhibitors might travel through the bloodstream, squelching metastases. When the large tumor was removed, it would no longer be a source of inhibitors, allowing the tiny metastases to proliferate.

Pub Date: 5/03/98

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