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Report drives up cancer drug stock

The stock of a company developing a new cancer treatment leaped from $12 to $85 at one point Monday, even while doctors cautioned against getting too excited over something that has been tested only on mice.

Cancer experts warned that while the approach is promising, treatments that look spectacular in lab animals almost never work so well in people.

"It's a very exciting observation in animals," said Dr. Bruce Cheson of the National Cancer Institute. "That's a long step from curing cancer in people."

The treatment involves two newly developed drugs, called angiostatin and endostatin, that are designed to choke off tumors' blood supply. Scientists watched mice with huge tumors respond dramatically to these injections. Their tumors shrank and then went away, and it seemed to work for all sorts of cancer.

The drugs were created by Dr. Judah Folkman at Children's Hospital in Boston, whose team pioneered the concept of attacking cancer by blocking its ability to grow new blood vessels.

While his results have been written about frequently and are widely known to cancer specialists, a New York Times article about the work triggered a new round of enthusiasm.

The article and the resulting publicity had a stunning effect on the stock of EntreMed Inc., the Rockville, Md., company founded to develop angiostatin and endostatin. The stock, which had traded at $12 on Friday, hit $85 at one point Monday. The company's stock closed at $51.81\.

The New York Times article quoted Nobel laureate James Watson, co-discoverer of the structure of DNA, predicting Folkman's approach will be a cure for cancer. Several cancer experts said Monday they hope Watson is right, but they doubt it.

"I am real skeptical that Folkman will be curing patients with these drugs," said Dr. Mark Ratain of the University of Chicago. "It would be wonderful if that happens. Oncologists will be looking for jobs if it's that simple."

However, many doubt it will be that straightforward. Several said that too often they have seen the medical profession, along with the news media and public, grow giddy over apparent cancer breakthroughs that fail to pan out in real life.

Examples include interleukin-2, interferon and monoclonal antibodies. All of these treatments were subjects of exuberant speculation when developed over the past 20 years. Even though they worked wonderfully in animals, they have turned out to be of modest benefit in people.

"While nothing would please me more than for these to work as well in humans as they do in mice, the experience of the field would argue it may not be quite so simple," said Dr. Louis Weiner, head of medical oncology at Fox Chase Cancer Center in Philadelphia.

Dr. Robert Mayer of the Dana-Farber Cancer Institute in Boston worried about the effect of such unbridled enthusiasm on people with cancer.

"The patients are the losers when all of this dangled in front of them, and it turns out to be nothing," said Mayer, who is also president of the American Society for Clinical Oncology.

Of course, no one knows if Folkman's discoveries will turn out to be nothing. Indeed, several said their hunch is it will eventually have some role in cancer treatment, although it may have to be combined with other medicines.

The treatment works in mice by stopping the growth of new blood vessels that must sprout if tumors are to grow and spread. The mice, however, are genetically identical inbred strains that carry tumors that have been implanted in them.

While these are the standard early proving ground for new drugs, experts caution that the animals are very different in biology and immune reactions from humans who grow tumors that have arisen from their own breasts or prostate glands.

Certainly no one knows whether human cancers will be so easily thwarted. Among other questions to be answered:

Can angiostatin and endostatin, which are normal proteins, be duplicated through gene splicing? Scientists say these are large proteins and so are technically difficult to make. The company hopes to have enough for human testing in 12 to 18 months.

Will humans be able to tolerate them? Interleukin-2, which mice could stand in large doses, turned out to be toxic in people and has to be used sparingly.

Will the drugs have side effects that make them hazardous when given for many years, as some envision them being used?

What happens to the body's ability to heal wounds? Presumably, anything that stops new blood vessel growth would also block this vital process.

The National Cancer Institute said Monday it is encouraged by preliminary research into endostatin and angiostatin and "has made it a high priority to move research forward on these compounds so that clinical trials in humans can begin."

Human studies probably won't begin until 1999, the cancer institute said. The compounds must be tested separately for safety and effectiveness in humans before they can be given in combination to patients. EntreMed said it will be 12 to 18 months before either of the drugs goes into tests involving human patients.

Several others drugs aimed at blocking blood vessels have already entered early stages of human testing, and researchers said that perhaps 50 in all are in various stages of development.

_ Information from Bloomberg News was used in this report.