Drug shows promise in lung cancer treatment
A recently invented drug powerfully shrinks tumors in lung cancer patients carrying a specific genetic marker, a discovery that physicians said will rapidly lead to the first effective treatment in a generation for the most lethal and widespread cancer.
The once-a-day pill, Iressa, was approved last May, but only as last-ditch therapy for patients with advanced lung cancer, because it worked only sporadically in clinical trials. A small percentage of patients experienced remarkable recoveries, with the drug extending their lives by a year or longer, and two Boston teams published studies yesterday pinpointing the patients who will benefit.
The impact will probably be immediate and dramatic: Researchers at Massachusetts General Hospital have already applied for a patent on a test that can pick out the patients likely to respond. Within months, lung cancer patients worldwide could get the drug from the moment of diagnosis, rather than having to first take the mostly ineffective and unpleasant chemotherapy now prescribed.
And those unlikely to benefit from it would be spared the time and cost of taking the expensive new drug, which is made by
Though only about 10 percent of patients respond to Iressa, that is still a sizeable number. Lung cancer kills about 157,000 Americans annually, many of them just a few months after their tumors are discovered.
"A small but substantial subset of patients will respond to taking one pill a day," said the Dana Farber Cancer Institute's Dr. Bruce E. Johnson, an author of one of the papers. "We think that's pretty dramatic. We're talking about more than 10,000 patients a year in the US."
The new studies are an important advance in the effort to fashion cancer drugs to target the genetic characteristics of individual patients.
"I think its the new paradigm in cancer treatment, and it's the first example of it in a major human cancer," said Dr. Matthew Meyerson of Dana Farber, who with Dr. William Sellars, is running a large-scale local effort to similarly fine-tune other cancer drugs.
In addition to the Iressa studies, California biotechnology giant
The Iressa findings solve a medical mystery that has long nagged cancer researchers. Since human studies of the drug began almost four years ago in patients with non-small-cell lung cancer, the type that accounts for about 85 percent of lung cancers, most of the patients getting Iressa died rather fast.
But 13.6 percent saw their tumors shrink by at least half, and there were stories of miraculous rebounds from cancer wards around the country. Patients reported few significant side effects, though some experienced minor rashes and fevers.
Doctors had no idea which patients would respond. However, they were convinced that some DNA mutation in the cancer cells of the improved patients would provide an answer.
Now they have found that telltale DNA sign, according to the new research, published in two leading journals, The New England Journal of Medicine and the online edition of Science.
"It turns out that the mutations we found make the cancer cells more sensitive to the drug, almost 10 times as sensitive," said Dr. Daniel Haber, director of the Mass. General Cancer Center.
Iressa works by latching on to epidermal growth factor receptors, or EGFR, on the surface of lung cancer cells, thereby jamming the replication process that allows cancer to flourish.
After studying tumor samples from patients, the researchers found that particular DNA mutations in the gene for EGFR in the cancers of certain patients intensified Iressa's power. The finding was corroborated in four experiments in which researchers studied dozens of tumor samples.
Scientists from Brigham and Women's Hospital, Harvard Medical School, and the Broad Institute at the Massachusetts Institute of Technology also collaborated on the research.
Next, researchers plan to conduct clinical trials on Iressa when it is used as an initial, or first-line, treatment, as well as in combination with other treatments, the final proof needed to establish its efficacy.
"I think it is fair to say that patients who have the mutation in their tumors are highly likely to have a substantial response to Iressa that will improve their symptoms and considerably prolong their survival," said Dr. Thomas Lynch of Mass. General, also an author of the studies.
Lynch and his colleagues have already applied for a patent on a screening test, and he said it should be available internationally within months.
Dr. Harmon Eyre, chief medical officer of the American Cancer Society, called the new studies a major step, though he cautioned that "this was a very small trial and we look forward to seeing the results repeated in additional, larger trials."
But both bedside doctors and laboratory scientists agreed that the new work represents a significant achievement in the effort to design smart cancer drugs to exploit recent advances in understanding the human genome, life's blueprint.
"This data validates and reinvogrates the concept, or the approach, of targeted therapy," said Dr. Frederic Kaye of the National Cancer Institute.
But it is better to prevent lung cancer in the first place, he said. "The key thing is not to smoke, and if you do, stop smoking."
Raja Mishra can be reached at rmishra@globe.com.
