New leukemia drug gets FDA approval

The federal government Thursday approved the first in a new class of designer cancer drugs created to hone in on specific molecular targets, leave normal cells alone, and avoid the horrific chemotherapy that has characterized most cancer treatments until now.

"This new drug, we believe, is the picture of the future of cancer treatment," said Dr. Richard Klausner, director of the National Cancer Institute.

The drug represents advances in understanding cancer biology, and is a harbinger of a new wave of emerging experimental drugs tailored to the genetic makeup of specific types of tumors.

"It is very hard to describe what a different world this is from just five or six years ago," Klausner said, speaking at a news conference.

The drug, Gleevec, also known as STI571, is a treatment for chronic myelogenous leukemia, or CML, a life-threatening disease in which too many white blood cells are produced.

Gleevec, an oral medication -- four pills taken once a day -- works by disrupting a cellular signal to the body to produce an enzyme that makes white blood cells proliferate.

The medication causes only minor side effects, among them mild nausea, puffiness around the eyes and muscle cramps.

While the disease is relatively rare -- diagnosed in about 6,000 Americans annually -- the drug represents a breakthrough as the first to go after a target that is "not just in a cancer, but a target responsible for the cancer," Klausner said. He said it could play a role -- although probably not as dramatic -- in as many as 20 different types of cancers.

To be sure, researchers cautioned that because the drug has been studied for less than three years in humans, they still don't know the long-term effects of the medication -- whether it will cure the disease, or simply hold it in check.

Still, the results have left scientists ebullient.

"I had one patient who was literally planning her funeral, and now she's out playing with her grandchildren," said Dr. Brian Druker, director of the leukemia center at the Oregon Cancer Institute in Portland, who developed the drug with its manufacturer, the Swiss company Novartis Pharmaceuticals Corp.

The Food and Drug Administration licensed STI571 on its "fast track" approval process after clinical trials showed that the drug restored most patients' blood counts to normal, and fairly quickly.

UCLA's Jonsson Cancer Center was among the sites that conducted the earliest clinical tests of the drug, and one of its researchers, Dr. Owen Witte, was involved in studying the genetic mutation that causes the disease.

This form of leukemia results from a chromosomal abnormality, first discovered in CML patients in 1960, dubbed the "Philadelphia" chromosome. It is this chromosome that "turns on" the blood enzyme that causes the white cells to multiply.

CML generally progresses slowly, and typically occurs in people who are middle-aged or older. It progresses in four stages, the first without any symptoms. As the disease develops, sufferers experience fatigue that won't go away, a feeling of lethargy, fever, loss of appetite and night sweats.

Conventional treatments until now have involved chemotherapy and bone marrow transplantation.

Druker said the drug has been studied in more than 6,000 patients worldwide since June, 1998.

Druker described a group of 532 patients he studied who started on the drug three years after diagnosis, who had failed conventional therapy, but had not yet progressed to the more advanced stages of the disease.

After starting the drug, "close to 90 percent had their blood counts returned to normal, and -- in about one-third -- we can't detect any traces of leukemia in their bone marrow," he said. "Fewer than 2 percent stopped because of side effects -- compare that to chemotherapy.

"You won't hear doctors use the word "miracle' very often, but when you see results like these in some of these patients, you start to hear that word," Druker added.

The drug is less effective, however, when given to those who have already advanced to the late stages. It helps temporarily, but most patients eventually relapse, Druker said.

Klausner said that cancer researchers have been devoting their efforts toward identifying a range of new compounds with a similar mode of action.

For example, there are now 68 "targets" identified for breast cancer alone "for which we now have (drugs) about to go into clinical trials," he said.

Gleevec is expected to be available within two weeks. While expensive -- it will cost up to $2,400 a month -- Novartis officials said the company would establish a program to provide free or low-cost drugs to those who cannot afford it.