A so-called "leukemia pill" that produced stunning benefits in the treatment of chronic myelogenous leukemia (CML) is showing similar effectiveness against chronic cases of gastrointestinal stromal tumors (GIST), a rare cancer.

The drug, which targets only the cancerous cells, is the first effective nonsurgical therapy against these tumors, which spread readily and are generally fatal within 20 months.

Charles Blanke, MD, director of gastrointestinal oncology at Oregon Health & Science University in Portland, Ore., presented findings at the meeting of the American Society of Clinical Oncology. Phase II clinical trials began in July 2000 at OHSU, Dana Farber Cancer Institute in Boston, Fox Chase Cancer Center in Philadelphia and Helsinki University Central Hospital in Finland.

The drug, STI-571, goes by the brand name Gleevec. In GIST, the orange-ish capsule interferes with the errant enzyme, called c-kit, that sends a cell's nucleus into abnormal overdrive, creating the uncontrolled growth of gastrointenstinal stromal tumors.

Of the 148 patients taking Gleevec, 59% achieved remissions, which have lasted from 4.5 to 10 months. So far, none have relapsed. Patients ranged in age from 18 to 83 years.

Blanke said that more follow-up was needed, as these patients have only been followed for up to 10 months. "We have no idea what ultimately it will mean for patients, but obviously, it’s good news for now," he says.

"It is really the beginning, hopefully, of a new wave of treatment of cancer. . . to drugs that are directed against the specific abnormalities present on cancer cells," says Herman Kattlove, MD, a medical editor with the American Cancer Society and a former practicing medical oncologist.

The tumors’ shrinking occurred after four weeks for some patients; for others, shrinkage has been gradual and continuing.

As the tumors break down, patients have felt better, says Blanke: they discontinue narcotics for abdominal pain, relish food, and regain the strength to leave their beds and resume a normal life. Side effects can include leg and eye swelling, as well as tumor bleeding, though the bleeding has occurred in just three GIST patients. Blanke thinks the bleeding is a signal of a response, that the tumor is shrinking. Such bleeding has not occurred in leukemia patients taking the drug.

Trudy Webb of Jefferson, Oregon felt she was on her deathbed last June when Blanke invited her to join the trial. "I could feel my tumor growing every day," says Webb, 49. Pressure from the 10-pound tumor against her lungs made it difficult to breathe.

But after one week of Gleevec, Webb could feel the tumor start to "melt away. I’m getting my physical strength and endurance back. This is absolutely wonderful, an absolute miracle." Her major side effect: troublesome fluid retention.

Newly revised figures from the National Cancer Institute estimate that Webb is one of 5,000 Americans suffering from gastrointestinal stromal tumors (GIST).

High-dose chemotherapy had been the usual treatment for invasive GIST, but the response rate is only 5% and the side effects are extreme. In general, solid tumors do not respond well to chemotherapy.

"I think of STI as a guided missile," says Blanke. Traditionally, therapies kill healthy cells along with the cancerous ones. "But this is targeted at the specific aspect that makes cancer cells behave so badly. By targeting them, we hope the drug will be less toxic and more effective."

On Thursday, the US Food and Drug Administration announced its accelerated approval for Gleevec’s sale in the United States for the treatment of chronic and acute-phase CML. The approval came less than three years after the first clinical trial of STI-571. Outside the US, Gleevec has only been approved in Palestine and Korea.

According to the manufacturer, Novartis Pharmaceuticals, clinical trials of Gleevec recently closed for small-cell lung cancer and a form of prostate cancer, and researchers are reviewing the results. Clinical trials are still open for enrollment, however, for a rare brain cancer called glioblastoma, and for gastrointestinal stromal tumors.

Novartis has set up a toll-free information line about Gleevec for medical professionals and consumers for general information on the drug, clinical trials, and help with understanding insurance reimbursement or qualifying for patient assistance.

A scientific spokeswoman said the company is committed to every CML patient who needs the drug having access to it. The number is 1-877-GLEEVEC (1-877-453-3832). Because the treatment is a pill, it is not covered by Medicare, though some members of the U.S. Congress may push for an exception in Gleevec’s case.

"We are gaining more and more control over the cancer problem each year, and this is a particularly graphic demonstration of it," says David Baltimore, PhD, president of the California Institute of Technology in Pasadena. Baltimore, a biologist, is the 1975 co-winner of the Nobel Prize winner for his discovery of an enzyme, reverse transcriptase, that permits retroviruses to replicate — an important factor in later understanding of cancers. "For a drug that has such a dramatic effect on cancer to have such little effect on the whole normal body is miraculous."

But Gleevec likely is not the cure for cancer, emphasize OHSU’s Blanke and Druker. Chronic myelogenous leukemia, the intestinal tumors and the brain cancer glioblastoma are each driven by a single enzyme. Gleevec can disable these three enzymes, which are similar in structure.

But most other cancers are more complicated, say the scientists, with multiple abnormalities working in concert.

"Those enzymes may be present in those cancers, but ‘present’ doesn’t necessarily mean critical to the cancers’ growth or survival," says Druker. Locking up one troublemaker in a chemically complex system wouldn’t create a response. "It would be the difference between cutting off a finger," Druker says, "and putting a stake through the cancer’s heart."