LEUKEMIA CURE? UCLA TESTS SHOW DRUG'S TREMENDOUS POTENTIAL.

Byline: Phil Davis Staff Writer

Patients at UCLA were among the first in the world to get an experimental drug that appears to deliver a knockout punch to a specific type of leukemia.

The drug, STI-571, is the first in 13 years to show tremendous potential in early clinical testing as a therapy for chronic myelogenous leukemia, said UCLA's Dr. Charles Sawyers, one of the authors of the study to be presented Sunday at the American Society of Hematology conference in New Orleans.

STI-571 targets a mutant protein in a cancer-causing gene specific to chronic myelogenous leukemia, a cancer of the blood that strikes more than 4,300 Americans each year.

All 31 patients taking at least 300 milligrams a day have had normal white and red blood cell counts for as long as eight months, said Dr. Brian J. Druker of the Oregon Health Sciences University. Moreover, 30 of them had normal blood counts within a month of beginning treatment.

Most importantly, the medicine apparently eliminated cancer-causing cells in three patients and reduced their number in six others.

``It's a smart drug,'' Sawyers said. ``It knows what's wrong with the leukemia cells, and it attacks that. It goes right to the heart of the problem and shuts it off.''

Traditional therapy for the cancer calls for the use of drugs such as interferon, which has serious side effects, or a risky bone marrow transplant. The worst side effect of STI-571 reported so far is mild nausea, which goes away after the patient eats.

That's rare in a Phase I clinical trial, which usually focuses on finding an acceptable dose that won't seriously harm a patient.

``We still haven't found a dose that is too high,'' Sawyers said.

The first test was so successful that drug manufacturer Novartis is seeking U.S Food and Drug Administration approval to accelerate the second phase of testing, which is already under way in the University of California, Los Angeles, as well as centers in Portland, Ore., and Houston Texas.

The drug already has had a huge impact on the few people who have taken it.

Seth Shapiro, a 35-year-old Los Feliz resident, was diagnosed with leukemia in April 1998. He said the extreme drowsiness associated with interferon treatments made it nearly impossible for him to continue designing computer software for the Walt Disney Co. in Burbank. The interferon wasn't working well, and the odds of finding a suitable bone-marrow donor were slim.

``It was grim,'' Shapiro said. ``I thought, Jesus, if I have to be on this for the rest of my life, it won't be much of a life at all.''

He joined the STI-571 trial in February, and within three weeks his white blood cell counts had dropped back to normal levels.

I'm still tired, but it's manageable,'' Shapiro said. ``It worked. And it's definitely worth it. There are people who are on this who have had complete cellular remission.''

The drug only works on CML, which accounts for about 4,300 of the 30,000 new cases of leukemia in the United States each year, according to the Leukemia Society of America.

Nobody knows yet if the new medication's effects will last or whether the cancer will develop resistance to it. But researchers said it is an important study even if the effects turn out to be short-lived.

The reason: The medicine is designed to stop a certain enzyme that triggers the disease. Doctors said this approach breaks new ground by targeting the particular biological defect that causes the cancer.

``We think this is a real break-through,'' Sawyers said. ``This will add new hope to leukemia treatments. We're learning how to treat this cancer in a safer way.''

UCLA's Jonsson Comprehensive Cancer Center is seeking CML patients for the second phase of testing. Anyone interested in the study may call [phone].

Wire services contributed to this story.