Gleevec OK'd by FDA; effectiveness hailed

By Richard Palmer

Relatively few people had heard of the orange pills known as Gleevec (or Glivec or STI-571) before this month.

That all changed Thursday, May 10, when U.S. Health and Human Services Secretary Tommy G. Thompson held a press conference to announce the federal Food and Drug Administration had approved Gleevec for the treatment of chronic myeloid leukemia.

Novartis Pharmaceuticals, the maker of Gleevec, had applied for approval exactly 10 weeks before approval came - one of the fastest reviews ever for a cancer drug. The FDA action came after it reviewed three separate studies involving more than 1,000 patients.

As details of the effectiveness of Gleevec and its implications became known, the announcement became Big News. CNN cycled the story every half hour throughout the day. The Associated Press wrote and updated the story several times, and the news made the front page of newspapers nationwide.

While the focus was on Gleevec’s effectiveness against CML, reports also touched on Gleevec’s effectiveness against gastrointestinal stromal tumor, which the media persisted in calling “a rare stomach cancer.”

Three days later in San Francisco, at the annual meeting of the American Society of Clinical Oncology, Dr. Charles Blanke appeared at a press conference to announce that the socalled “leukemia pill” had stunning results against gastrointestinal stromal tumor.

The next day (Monday), the Oregon Health Sciences University oncologist stood before thousands of his peers at ASCO plenary session and outlined the findings of his study on Gleevec vs. GIST.

In a phase II clinical trial involving 139 patients, the cancer had gone into remission in 59 percent of the patients, and 90 percent of patients reported major signs of clinical improvement – going off pain-relieving narcotics, returning to work, resuming activities.

So far, Blanke said, none of those who went into remission have relapsed, this over a period of 4 ½ to 10 months.

"This is exciting news, not just because these results validate the theory of targeted therapy, but because these patients have no other options," said Blanke.

As reported by CBS, the success of Gleevec represents a sudden reversal of fortune for people diagnosed with GIST. Until now, the disease has resisted everything doctors have hit it with. Usually starting in the connective tissue of the stomach or small intestine, it strikes any of the organs in the entire length of the gastrointestinal tract. These tumors are prone to spread to other organs and are almost always unresponsive to chemotherapy or irradiation. Some tumors can be removed by surgery, but they usually return. The disease has been invariably fatal – before Gleevec.

"Late-stage GIST patients often have withstood multiple surgeries and have generally exhausted their options,” Blanke told Novartis, the maker of Gleevec. “If Gleevec continues to demonstrate efficacy and safety in this setting, it may represent a major breakthrough."

It is a breakthrough that may affect more people than once thought. GIST is a type of cancer that was only recognized in the past few years; before that it was considered a gastrointestinal leiomyosarcoma. Blanke told the San Francisco Chronicle that government scientists have recently gone back over tissue samples and revised upward their estimate of the numbers of GIST cases each year, from 1,200 to between 5,000 and 10,000.

The phase II trial began in July 2000 and is being conducted at four cancer centers — OHSU, Dana-Farber Cancer Institute in Boston, Fox Chase Cancer Center in Philadelphia, and Helsinki University Central Hospital in Finland. Patients were equally randomized to either a 400 mg or 600 mg daily dose of Gleevec. At three months or less, responses were observed in 54 percent of patients.

Dr. Allan T. van Oosterom, professor of medicine at the University of Leuven in Belgium and president of the European Organization for Research and Treatment of Cancer (EORTC), told WebMD that a smaller study of 36 patients with GIST suggests that the most effective dose is actually 800 mg.

"I have two patients who didn't respond at 400 mg; we increased to 800 mg and now they are responding," van Oosterom told WebMD.

Blanke told WebMD that several other cancers have similar biological mechanisms, and OHSU is beginning a trial in small-cell lung cancer patients. Other researchers are testing the drug in hormone refractory prostate cancer and glioblastoma brain tumors.

Novartis has set up a toll-free information line about Gleevec, 1-877- GLEEVEC (1-877-453-3832), for medical professionals and consumers. It also offers help qualifying for patient assistance.

Editor’s note: Some figures cited by Dr. Blanke at his May 14 presentation before ASCO do not agree with abstracts on the ASCO Web site, which were submitted months ago and are