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Chemotherapy Agent Shows Promise for Lung Cancer Patients - 2004-04-30

Medical researchers have achieved a scientific breakthough that promises to successfully treat, if not cure, lung cancer and other cancers that have had a poor prognosis. The discovery involves a chemotherapy agent that works extremely well in only a small percentage of lung cancer patients, but it could lead to other drugs to successfully treat a wide range of cancers.

Lung cancer is among the most lethal forms of cancer. It's hard to detect and, by the time it is found, the disease is usually in an advanced stage. Few patients are still alive five years after being diagnosed.

A three-year-old drug, known by it's brand name Iressa, works in about 10 percent of patients with the most common forms of lung cancer, known as non-small cell cancer. In those patients, Iressa completely arrests lung tumor growth and even causes some tumors to shrink. Iressa also causes very few side effects.

?I think it's the best new hope yet,? said Matt Meyerson who is senior author of a paper published in the journal Science that reports on a study that investigated why Iressa works so dramatically in some lung cancer patients and not at all in others.

Researchers at Dana Farber Cancer Institute in Massachusetts, led by Dr. Meyerson, looked at the genetic material of patients who responded positively to Iressa. They found mutations that made the drug effective.

Investigators at nearby Massachusetts General Hospital conducted a complementary study published in the New England Journal of Medicine. The director of the hospital's cancer center, Daniel Haber, headed the research team.

?These mutations are quite remarkable in that they work better than the normal protein, so they make the cancer cells grow better. But at the same time they make them more sensitive to the drug,? he said. ?So, it's a bit of a double edged sword. And we now think we understand why patients who have these specific kinds of lung cancers respond so well to the drug.?

Dr. Haber says Iressa, also known as gefitinib, works by blocking robust tumor growth in patients, and shuts down the process.

Dana Farber Institute Cancer Institute researcher Matt Meyerson says the discovery has implications for the development of other chemotherapy drugs.

?I think it makes the same point for cancer more broadly that targeting the genes mutated in cancer is a good way to get new cancer treatments, and that we should be able to do this across many cancers in a really systematic way over the next (several) years,? Mr. Meyerson said.

Cancer specialist Mark Green, of the University of South Carolina in Charlston, says the discovery has a number of implications.

?I consider the report in the New England Journal as of real interest and quite significant both in terms of individual patients with lung cancer and the opportunity to potentially predict who will have a very worthwhile clinical benefit and response to gefitinib therapy and then, more broadly, as a paradigm for taking us to the next level in targeted therapy for people with malignancies in general and solid tumors in particular,? Mr. Green said.

The findings of the two studies are what researchers call a "proof of principal," meaning they had a theory, they proved it, which bolstered their notion that it should work in other cases, with other cancers.

Dr. Haber of Massachusetts General says a number of new drugs will be coming on line shortly that block overractive growth proteins in various cancers. He says the findings from of his work reported in the New England Journal, and the research posted in Science, will help investigators focus the drugs on specific targets.

?It's not always been totally clear in which patients and with what kind of cancers should these drugs be used to treat,? Dr. Haber said. ?I think this kind of tells us that there are certain molecular markers that we can rely upon and we should look for to identify which patients are most likely to respond to these new drugs.?

By knowing who does and doesn't respond to anti-cancer drugs, doctors and patients won't waste their time on chemotherapy drugs that don't work.

Meanwhile, Iressa has been approved in the United States by regulators and will soon be widely available for the treatment of non-small cell lung cancer.