A deadly disease, a promising drug
Iressa was a "targeted" cancer drug with no target. Until last week, that is. New evidence suggests that the drug may attack the most common form of lung cancer. Technically known as non-small cell lung cancer, the disease hits 140,000 people a year; it's deadly and doesn't respond well to standard chemotherapy.
The theory behind Iressa is that it homes in on a molecule that's essential to cancer growth. It was disappointing in its early trials, however, helping only a fraction of patients who tried it. Even that would have been OK if doctors knew which patients would respond and which wouldn't, but they had no way of knowing that. Since such specialized cancer drugs are expensive and often have toxic side effects, Iressa was considered impractical as a general lung cancer treatment. The government approved it only as a last-ditch therapy for patients who had exhausted their other options and were still getting sicker.
Possibilities and glee. Now researchers think they've identified the molecular target. Some cancers have a mutated version of a growth molecule called EGFR, and in patients with that mutation Iressa works spectacularly well, according to papers just published in both Science and the New England Journal of Medicine. There's already a test for the mutation, which could identify tens of thousands of people who would otherwise have had little hope. In addition, there are patients with other forms of the disease who might be suitable candidates. The numbers in these two studies are small. But normally cautious researchers are having trouble disguising their glee. "When you actually know what you're aiming at, it opens up a world of possibilities," says Alan Sandler, a lung cancer specialist at Vanderbilt University Medical Center who worked on some of the original Iressa studies. "We're really happy, about as happy as I've been in 20 years of this kind of research," says Bruce Johnson, a medical oncologist at Dana-Farber Cancer Institute in Boston and a coauthor of the Science paper. "I think our patients are going to be really happy, too."
The mutations (there are actually several) are in part of the EGFR molecule that appears to stimulate growth signals in the cancer cell. Scientists speculate that Iressa binds more strongly to the mutations than it does to the normal molecule and thus blocks the growth signals more effectively. In the 10 percent of patients who respond to the drug--and who now seem to have the key mutations--it's at least 80 percent effective. The average patient has had his tumors shrink and symptoms improve for six months, and for many these improvements have lasted several years. "So that's at least 10,000 patients every year that we can help that we couldn't help before," says Johnson. In addition, another 20 to 30 percent of patients on Iressa remain stable--their cancers don't shrink but they don't get any worse--and these people may turn out to have the mutations, too. If so, and studies on these people are just getting started, the drug may turn out to hit the target for more than a third of all patients.
This story appears in the May 10, 2004 print edition of U.S. News & World Report.
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