ORLANDO -- On Nov. 8, 2000, George Darr got news that would turn his life upside down.

A routine blood test revealed that the Portland, Ore., resident had chronic myeloid leukemia (CML). He soon realized that the crushing fatigue he had written off to his killer work schedule as manager of a Northwestern U.S. power supplier was in fact a symptom of the cancer.

Darr signed up for a study of a new drug called Gleevec . Three weeks after he started taking the drug, the white blood cells in Darr's bloodstream stopped multiplying like mad, and his energy level soared.

"I was incredibly lucky," he says now about getting Gleevec , a drug that oncologists consider a revolutionary treatment for CML, a disease that strikes 5,000 people in the USA each year. Lead researcher Brian Druker of the Oregon Health & Science University unveiled findings on Monday from a new study of Gleevec during the annual meeting here of the American Society of Clinical Oncology (ASCO).

The findings suggest the drug erases many signs of the leukemia when given to people with an early form of the disease. A second study presented Sunday confirms that the drug can melt an advanced form of a rare stomach and gut cancer.

"These results are incredible," says ASCO president Larry Norton. He and other cancer specialists say Gleevec is one of the first drugs to target the molecular defect in cancer, an approach that may very well offer people such as Darr a long-lasting reprieve from cancer. 'Not a universal cure'

Still, oncologists such as Richard Silver at the Weill Medical College of Cornell University say they'll wait to see if Gleevec 's early promise pans out. He says the drug probably will not work for all patients with CML or stomach cancer. And Gleevec may not work for other kinds of cancer at all. "It's not a universal cure," he says.

Still the new findings presented this week add to previous reports of Gleevec 's prowess. Researchers already had shown this drug could slow the progression of a very advanced form of CML, a disease that causes an explosion of white cells in the blood and bone marrow.

Druker wondered how well the drug would perform when given to people who had an early form of the disease. Druker and his colleagues recruited more than 1,000 men and women who had just gotten a diagnosis. Half the patients got Gleevec ; the rest got the standard drug therapy of interferon. After about a year, the team found that just 4% of people taking Gleevec had cancer that had gotten worse. In contrast, 19% of the interferon patients had cancer that had progressed.

Scientists who study this leukemia know that cancer cells can vanish from the bloodstream yet still lurk in the bone marrow. So Druker and his colleagues looked at bone marrow samples: They could find no evidence of leukemic cells in 68% of the people taking Gleevec . Just 7% of people taking interferon got the same good news. Fewer side effects

Still, this test doesn't find every cancer cell hiding in the bone marrow. It's likely that a few leukemic cells remain. But if the drug hammers most of the cancer cells in the body, it offers a major advance over interferon, Druker says.

And Gleevec gave Darr and others like him a boost without the side effects that often accompany interferon treatment. Druker says that 23% of the people in the study assigned to the interferon group had to stop taking the drug because it made them feel as though they had the flu all the time. Less than 1% of people taking Gleevec had to stop taking the drug because they suffered from nausea or skin rashes.

Darr felt so much better after getting Gleevec that within weeks he embarked on a new project at his job. Darr was instrumental in the Bonneville Power Administration's plan to purchase 1,000 megawatts of energy harvested by non-polluting wind turbines. Darr says there's no way he would have done the project without this drug.

Researchers don't really know whether Gleevec will offer people such as Darr a survival edge. This study lasted only a year, but Druker hopes the drug eventually will annihilate the cancer, either by itself or by combining it with another treatment.

Gleevec is one of the first drugs to target a specific defect that causes the cancer. Unlike chemotherapy, which kills many cells in the body, even those that are not cancerous, Gleevec zeroes in on the leukemic cell. It works by blocking the action of an enzyme that cancer cells use to divide furiously. Without the enzyme action, the leukemic cell can't divide and eventually dies, Druker says.

Gleevec also targets another enzyme, one that tells gastrointestinal cells to divide like mad. A second report at the medical conference, this one presented by Margaret von Mehren, a cancer specialist at the Fox Chase Cancer Center in Philadelphia, confirms that Gleevec can knock back this kind of cancer as well.

Gastrointestinal stromal tumor is a rare form of stomach and gut cancer that strikes 5,000 people each year in the USA. In some cases, surgeons can remove the tumor, helping patients live longer. But in many cases, doctors couldn't offer patients with this cancer much hope -- until Gleevec came along.

In fact, the 147 patients in this study had already failed standard treatments such as chemotherapy or radiation, von Mehren says. Without the drug, they almost certainly would have gotten worse, she says.

But the team found that 63% of people in the study had tumors that had melted away by half, a sign that the drug had stopped the proliferation of these cells. Another 20% had tumors that didn't get larger.

In some cases, the reprieve from cancer didn't last. About 18% of the group that had originally gotten better went on to have growth in their tumor, she says.

And Gleevec doesn't seem to offer these patients a cure. "We've not seen anyone with disease that has gone away," she says. But the hope is that the drug has stopped the tumor cells from growing. If so, the disease may stay in place without getting worse.

More than 80% of patients in this study were alive at the end of the 15-month follow-up period. "This is truly remarkable," von Mehren says.

Michael Gordon, a researcher at the University of Arizona Health Sciences Center in Phoenix, agrees. He says about half the patients in this study would have died if they had not taken Gleevec . New beginnings

The drug seems to have given Raymond MacDonald of Whiting, N.J., a second shot at life. He had run through chemotherapy, radiation and other traditional forms of treatment, yet he had a grapefruit- size stomach tumor that kept growing.

Within a month of taking Gleevec , MacDonald's tumor had nearly vanished. And Gleevec helped him in another way. He says he got so sick on chemo that he lost 60 pounds. Now he has regained most of his weight and is out of a wheelchair.

"Most patients are leading normal lives," von Mehren says. The disease is still there, however, and it may come back.

MacDonald believes the drug pulled him back from the edge. "As far as I am concerned, it's a miracle that I'm still alive."
(USA TODAY, May 21, 2002)