TEST CAPSULE HELPS CHECK LEUKEMIA STUDY SHOWS CANCER PILL BIG SUCCESS.

Byline: Orith Goldberg Staff Writer

An experimental medicine that attacks a common form of adult leukemia shows ``mind-boggling'' results, even for some near-death patients, according to a UCLA study being published today in the New England Journal of Medicine.

The once-a-day-pill Glivec was used on 83 patients, including two San Fernando Valley residents, at the University of California, Los Angeles, in the first phase of chronic myelogenous leukemia, which strikes more than 10,000 people worldwide each year. The pill attacks a gene linked with the cancer.

``It's just mind-boggling that a pill can cause a patient near death with leukemia to go into remission and cause no side effects,'' said Dr. Charles Sawyers, a professor of medicine at the UCLA Jonsson Comprehensive Cancer Center who headed up the study. ``It's the most satisfying thing I've done in my life.''

Researchers say Glivec, developed by Novartis Oncology, acts as a signal transduction inhibitor, a new class of drugs that can interfere with cell signaling pathways implicated in tumor development.

Beginning in June 1998, researchers conducted studies at three sites - UCLA, Oregon Health Sciences University and M.D. Anderson Cancer Center in Houston.

Ninety-eight percent of those patients treated with a dose of 300 milligrams or more of Glivec had positive reactions, in which their blood counts returned to normal.

The most common side effects of the drug include nausea and diarrhea, researchers said.

Bob Ferber, 48, of Calabasas considers Glivec a miraculous drug that has given him back his life since he was diagnosed with CML in 1999 after he noticed fatigue, bruising and problems with his vision.

``I want people to know there's research out there that's working,'' said Ferber, a prosecutor with the Los Angeles City Attorney's Office handling animal-abuse cases.

``The big C was something I was afraid of like every other American,'' said Ferber. ``It's like everything you can imagine on TV and more.''

Chronic patients with CML experience skyrocketing white blood cell counts but generally exhibit no symptoms for three to five years.

The disease can then advance to the accelerated stage, during which white blood cell counts increase even more. The end stage of the disease, known as blast crisis, can be fatal within several months, researchers said.

Early testing of Glivec at UCLA focused on patients in the chronic stage of the disease who did not respond to standard treatments with the drug interferon.

Researchers also studied the effect of Glivec on patients in blast crisis - 38 had myeloid blast crisis and 20 had acute lymphocytic leukemia or lymphoid blast crisis.

Responses occurred in 55 percent of those with myeloid blast crisis, with four of those patients having their white blood cell counts returned to normal.

Seven patients with myeloid blast crisis continue to receive treatment and remain in remission from 101 to 349 days after beginning treatment, they said.

Of the 20 with lymphoid blast crisis or acute lymphocytic leukemia, 70 percent had a response, including four with complete responses, the researchers said.

All but one with lymphoid blast crisis or acute lymphocytic leukemia have relapsed, but doctors are encouraged by the temporary responses.

The Federal Drug Administration has fast-tracked Glivec for priority review, and the drug could be approved as soon as midsummer, officials said.

Dr. David Snyder, associate director of the hematology/bone marrow transplantation division at City of Hope in Duarte, has also been studying Glivec and said even in the advanced stages of CML there were significant responses to the drug.

``The benefit is that it's very well tolerated,'' he said.

However, Snyder also cautioned that patients relapse while taking the drug.

``No one is going to look to this by itself to treat these diseases,'' he said.

Ferber took other medications including interferon and hydroxy-urea until January 2000, when he found he was running out of options and that a bone marrow donor had been found for him.

``The doctor gave me a 60 percent chance to live,'' said Ferber, who was considering the transplant when he heard about the clinical trials on the drug Glivec.

Ultimately he became the last person to be included in that trial, he said, and the results initially wavered between good and shaky. Until now his body shows only slight evidence of the disease.

Some patients who participated in the studies said they were grateful to be included, adding that they believe the drug helped save their lives.

Peter G. Barnes, 54, of Northridge began the trials in February 2000, years after having been diagnosed with CML just before his wedding in April 1993.

Barnes, whose leukemia remained chronic for seven years, said he is in hematologic remission, in which his white blood cell count is considered normal.

``I think it's kept me on this Earth longer than I certainly would have been here without it,'' he said. ``I think that and my attitude working together saved my life.''

After his leukemia accelerated and other drugs no longer worked, Barnes moved into the most advanced blast crisis stage within a month. ``When I went into blast crisis, it was a whole new game,'' he said. He did everything he could to get into the clinical trials, and began his first dosage just over one year ago.

``After the first dose, the very next morning, I felt a difference and the difference was positive,'' Barnes said, adding that he did suffer side effects such as nausea and skin rashes that soon decreased.

In a matter of months, Barnes was in hematologic remission.

``I felt a sense of honor that I could be a part of something to help thousands and thousands of people survive a disease that is historically deadly,'' he said.

CAPTION(S):

2 photos

Photo:

(1 -- color) Bob Ferber of Calabasas says the cancer drug Glivec has given him back his life.

Evan Yee/Staff Photographer

(2) BARNES