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Some say clinical trials showing  

cancer research is headed forward 

SAN FRANCISCO — A leukemia drug that brought cancer into remission in most patients in clinical trials is generating extraordinary excitement among cancer specialists and patients as a gentler, more effective treatment that assures researchers they’re on the right track. 

The drug, called Glivec, or STI-571, and manufactured by Novartis AG, should be available for prescription as early as June 2001, researchers said as they presented their findings at the American Society of Hematology convention on Monday. 

Meanwhile, people with advanced chronic myeloid leukemia will be allowed to get the pill immediately by joining clinical trials that are already in progress, and newly diagnosed leukemia patients can get on waiting lists for new trials, which will be gradually expanded. 

“This drug is a major breakthrough. It will change the way we treat patients with CML,” said Dr. Hagop Kantarjian, who oversees one of the trials at the MD Anderson Cancer Center in Houston, Texas. 

Anyone diagnosed with leukemia should make every effort to get the new pill, rather than depend interferon, the common treatment for leukemia, said Edward Benz, president of the Dana-Farber Cancer Institute at Harvard Medical School, who was not involved in the research. 

“I think patients ought to find out if there’s a clinical trial and if they qualify for it,” Benz said. “This is not a miracle drug,” he added, but it is a model for future cancer study because it targets the cause of the disease without damaging other cells. 

“The results support the dream that so many of us in molecular biology have – that is, if you know the genetic abnormality, you can develop a better therapy,” Benz said. 

Leukemia, caused by an abnormal protein that is the product of an abnormal chromosome, affects about 10,000 adults worldwide each year. It leads to a huge increase in the number of white blood cells, which can interfere with the functioning of other organs. 

Glivec blocks a signal that the protein sends out. That effectively prevents the abnormal growth and production of other cancerous cells. 

So far, the Glivec trials have involved almost 3,000 patients around the world who have not responded well to interferon, a natural protein which must be injected. Interferon revs up the body’s immune defense but has side effects including pain, joint inflammation and flu-like symptoms. And while it can prolong a leukemia patient’s life by up to two years, about 20 percent of patients stop using it because of its side effects. 

Bone marrow transplants are the only proven way of curing leukemia, but these procedures carry a mortality rate of up to 40 percent, and are only successful in 55 to 65 percent of cases. Other drugs are used to maintain the health of leukemia patients, but don’t decrease the number of white blood cells or help make the blood normal again. 

Results analyzed for more than 760 of these patients in different stages of the disease were presented Monday. More than 530 people in the first phase of the disease were studied and in more than 90 percent of the cases, their blood was normal after six months of treatment. 

The drug also proved effective for many people with more advanced leukemia: 91 percent of the 230 patients in the second phase of the disease responded positively; of these, 63 percent saw their blood counts return to normal. In some, the cancer-causing chromosome disappeared. 

“The main thing is that I got my life back,” said Carol Stuckey, a 50-year-old mother of two from West Linn, Ore., who was diagnosed with CML seven years ago and was close to being in the final phase of the disease, when a patient only has months to live. 

She has been on STI-571 since December 1999, and said the treatment has helped her lead a normal life. “I have energy again. Just prior to taking the medication, I was totally drained. Within two weeks of taking STI, I had wonderful energy. I went Christmas shopping.” 

Stuckey had not responded well to interferon and had been unable to find a match in bone marrow donors. She said she sometimes has leg cramps or puffy eyes since starting to take Glivec, but that those are minimal side effects compared to the lack of energy she was experiencing. 

“The whole of cancer research has been to identify the differences between cancer cells and normal cells. That’s been the goal of cancer research and here it is,” said Brian Druker, an Oregon Health Sciences University researcher who was the principal developer of the drug. “I view it as a new era of cancer therapeutics. It’s the most effective treatment we know of for CML.” 

Researchers chose CML because they knew about the abnormal chromosome and its abnormal protein. Before they transfer the model — targeting a specific abnormality with minimal effect on healthy tissue — to other cancers, they must isolate the causes. 

“All the cancers that have been studied are accumulations of genetic abnormalities,” said Benz. “The trick will just be sorting through those, and each of those is a long, drawn-out process. That doesn’t reduce the significance of this. It means in other examples we’ll have to work harder to find the target.”