New drug shows early promise in many types of cancer

Wednesday, November 20th 2002, 12:00 am

By: News On 6

FRANKFURT, Germany (AP) _ A new drug designed to stop cancer by cutting off its blood supply has surprised experts by showing a tumor shrinkage rate unprecedented for a drug so early in its development.

In the first human trials, involving 23 people with terminal cancer, the tumors of one-quarter of the patients shrank by half or more.

Similar drugs have proved disappointing _ prompting no dramatic tumor shrinkage in early tests. Scientists say the latest results, presented Wednesday at a meeting in Frankfurt, will likely revive flagging enthusiasm for the approach.

``Any activity in this situation is very promising since everything else has failed. But we did not expect to see such a high number of responses in a range of cancers,'' said the study's leader, Dr. Eric Raymond, head of the early drug testing unit at the Gustave-Roussy Institute in Villejuif, France.

The drug, which does not yet have a name, is a newcomer to the field of anti-angiogenics _ drugs designed to damage tumors by attacking blood vessels that feed them.

Although it has been a major focus of research over the last decade, anti-angiogenesis has not lived up to its early research promise.

Such drugs have shown only slight benefit, indicating they might sometimes slow or even stop some tumor growth, at least temporarily. None of them prompted the kind of dramatic tumor shrinkage or disappearance that doctors look for, even in the first stages of human tests largely intended to see if medicines are safe.

``Initially, we thought that this drug would be an agiostatic agent that stabilizes tumors, rather than an agiotoxic agent that actively shrinks tumors,'' Raymond said. ``We were happily surprised ... it seems that the drug is killing the blood vessels into tumors, regardless of the tumor type.''

Tumors shrank by more than 50 percent in six of the 23 patients. The cancer stabilized in five other five people.

It is rare for a drug to show more than a 5 percent regression rate in early human trials, said Dr. Jaap Verweij, head of experimental chemotherapy and pharmacology at Erasmus University in Rotterdam, the Netherlands.

``Although this is not proven as a drug, this is fascinating,'' Verweij said.

Experts said they believe part of the reason the new drug seems so much more powerful than others is that it attacks from three directions instead of just one.

As well as blocking a protein involved in blood vessel growth called vascular endothelial growth factor, the new drug also interferes with two other blood vessel growth factors _ basic fibroblast growth factor and platelet-derived growth factor. Some scientists suspect those enzymes might do more than just support blood vessel growth.

The drug is being developed by Sugen, a subsidiary of the U.S. pharmaceutical company Pharmacia.

``The intriguing observations of so many individual tumor responses is surprising and tantalizing,'' said Dr. William Li of the nonprofit Angiogenesis Foundation in Cambridge, Mass.

``One possible reason is that those three growth factors may also serve as survival factors for cancer cells, as well as for angiogenesis. Hence, (the drug) may serve as a double-barreled assault against both tumor blood vessels and tumor cells.''

The early promise of the drug illustrates new thinking in cancer therapy, said Dr. Michael Caligiuri, chairman of cancer research at Ohio State University.

Scientists are amassing a wealth of knowledge about the way cancer works at the molecular level, from the first scrap of rogue DNA in a cell nucleus that starts the process to the devastating assault of metastatic cancer.

The next decade will see a shift of emphasis from conventional treatment toward targeting the cellular and molecular abnormalities at the heart of cancer.

Another advance in that direction was reported Wednesday: A study of mice found a recently developed targeted leukemia drug _ Gleevec _ could boost the effectiveness of standard chemotherapy in many types of cancer by enabling more of the medication to get inside tumors.