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For patients, cancer drugs spark elation, and anguish

Dean Gordanier, 54, is a tax lawyer, fitness buff, father of three and veteran of the roller-coaster ride of hope and despair that is a way of life for growing numbers of people with cancer, thanks to the promise, and the heartbreak, of new drugs.

Many of these "targeted therapies" are scientifically breathtaking. With names like Gleevec, Avastin, Iressa and the still-nameless SU11248, these drugs are the closest scientists have come yet to the holy grail - knocking out cancer cells without wreaking too much havoc on the rest of the body.

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Some target specific enzymes called kinases that act as switches that control cell functions. Others are monoclonal antibodies that attack markers on the surface of cancer cells. And some starve tumors by attacking proteins that make their blood vessels grow.

"I am so unbelievably excited about the science because it is like standing on the Nina, the Pinta or the Santa Maria. You can see the New World coming," says Dr. George D. Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute in Boston.

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Gordanier is excited, too, because these drugs have saved his life - twice. But he is wary as well. Like any seeming miracle treatment, targeted therapies are fabulous when they work. But because cancer cells are wily and can mutate, even the most promising drug may stop working.

In 1999, Gordanier went to his doctor with acid indigestion, which turned out to be a potentially deadly stomach cancer called GIST (gastrointestinal stromal tumor).

In January 2000, he underwent a drastic surgical procedure called a "Whipple," in which doctors removed the tumor, 90 percent of his stomach, his spleen, 70 percent of his pancreas and his transverse colon.

But by September, his pain and his cancer were back. Doctors tried chemoembolization, or squirting chemotherapy drugs directly into the blood supply of his tumors, which had now spread to his liver. It didn't work, and Gordanier simply "waited to die," as he wrote in his diary.

Then he got lucky, joining a clinical trial of Gleevec for GIST (now FDA-approved for chronic myeloid leukemia and GIST). "I have been saved by the bell," Gordanier wrote in his journal. "It looks like Gleevec will allow me to struggle on with a good possibility of a successful outcome, if you define success (as I do) as being able to live and work without pain and to enjoy each day as it comes and for what it brings."

But 18 months later, Gleevec had stopped working, as it does in about 75 percent of people after two years. Once again, death loomed until Gordanier's doctor referred him to Demetri, who suggested SU11248, from Sugen (now made by Pfizer) So far, it's working.

"It's a holding action," Gordanier says. "The cancers will mutate. But I will be alive as long as the doctors can keep one step ahead of the tumors."

But even when a new drug is successful by statistical standards, the effect in real life may be minimal.

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Patients should ask doctors to explain the figures they quote from studies. Usually, such figures are averages, which means that if a drug prolongs life by five months on average, some people may get 10 months or more, some barely any.

And if you're basing your decision on results of a few specific studies, ask exactly what those studies measured, cautions Dr. Sidney Wolfe, director of Public Citizen's Health Research Group, an advocacy group in Washington.

"You really want to know whether the drug is effective for treating the condition you have, not some surrogate end point. Lowering blood pressure doesn't count unless it decreases stroke," he says. It may not be compelling for a drug "just to shrink tumor size temporarily if it's not accompanied by increased survival."

Judy Foreman is a lecturer at Harvard Medical School.


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