By Judy Foreman, Globe Staff, 12/04/1999

In a dramatic demonstration of the principle that targeting drugs to specific molecules can make cancer treatment both safer and more effective, researchers said yesterday that a new leukemia pill has proved 100 percent effective in a small, early test.

It also had no serious side effects, they said.

The researchers found that a drug called STI-571 triggered a normalization of blood counts, indicating remission, in all 31 patients tested. All patients had chronic myelogenous leukemia and all had failed to improve on interferon, the standard treatment.

Interferon causes numerous side effects, including pain and inflammation of the joints.

Overall, about 30,000 Americans will be diagnosed this year with some form of leukemia, a blood cell cancer; of these, about 4,500 have the form known as chronic myelogenous leukemia.

The 31 patients whose blood counts were normalized - meaning their white blood cell counts dropped back into the healthy range - took 300 milligrams a day of the drug, and some also showed reduction in cancer-causing cells.

The drug, made by Novartis Pharmaceuticals, appeared to eliminate cancer-causing cells completely in three patients and reduced their number significantly in eight, said the leader of the research team, Dr. Brian Druker of Oregon Health Sciences University in Portland, in a telephone interview yesterday.

The news, scheduled to be released tomorrow at a meeting of the American Society of Hematology in New Orleans, leaked out yesterday and had scientists buzzing.

These findings "are very encouraging," said Dr. Richard Klausner, director of the National Cancer Institute. "I congratulate these investigators on pushing forward the field of rationally targeted cancer therapy."

"It's very exciting proof that rational drugs can be developed to target the root causes of a cancer," said Dr. Jerome Groopman, chief of experimental medicine at Beth Israel Deaconess Medical Center.

"Prior to this, therapy has been like carpet bombing, just blasting away indiscriminately, killing normal cells along with white cells.

"This allows for the equivalent of a smart bomb which targets just the leukemia and spares healthy tissue."

Calling the results "very exciting," Dr. Harmon Eyre of the American Cancer Society said it is rare to see this kind of a response in preliminary safety testing of experimental drugs.

"The scientific community is very excited," added Dr. David A. Scheinberg, chief of the leukemia program at Memorial Sloan-Kettering Cancer Center in New York. "This is a unique disease in which we have a very good understanding of what causes it," Scheinberg said.

"We know the gene and what the gene does. And by understanding what the gene does, we can develop drugs to go after it directly."

Scheinberg cautioned that it remains to be seen whether the new drug, which caused only minimal side effects, will remain safe if patients take it indefinitely. So far, patients have been taking it for only about eight months.

In chronic myelogenous leukemia, two chromosomes become entangled and the spot where the crossover occurs creates a unique gene. That gene makes an enzyme called BCR-ABL, which causes white blood cells to proliferate, the hallmark of leukemia.

Unlike many drugs, which through sheer trial and error turn out to be useful against a particular disease, a "rationally designed" drug is made to attack a specific target, in this case, the BCR-ABL enzyme. By blocking it, scientists prevent cells from getting the growth signal.

Since the gene that makes BCR-ABL occurs only in chronic myelogenous leukemia, the Novartis drug theoretically should not work against other cancers. But the concept proved in the study - that a drug can be targeted to a feature specific to cancer cells - is widely applicable.

In addition to the 31 patients whose cases will be reported on in detail tomorrow in New Orleans, another 30 have been studied so far at Oregon, the University of California at Los Angeles, and at M. D. Anderson Cancer Center in Houston, said Druker, though results are not available. This study was designed primarily to test safety with increasing doses. Another round of testing will begin next month that will include 200 patients worldwide.

Druker said he has been gratified by being able to help patients whose doctors had told them they "did not have much time left."

When he started the research in June 1998, giving patients as little as 25 milligrams a day of the drug, he "didn't see much response," he said. "By the time we got to September, we started to see improvement at 140 milligrams, we started to see improvements in blood counts.

"By January, I was able to say with confidence to patients starting on the study that I was certain their blood counts would improve. By March, I was able to say I'd be surprised if their counts didn't normalize," he said.

"What has been so dramatic is that patient after patient has told me that we have restored their future."