The US Food and Drug Administration (FDA) today announced approval of Gleevec (formerly STI-571 or Glivec), for use in treating chronic myeloid leukemia (CML). There are about 5,000 new cases and 2,300 deaths from CML in the US every year.

The drug’s approval marks one of the fastest instances ever for a cancer drug to go from being tested in initial clinical trials to being available to patients. Human trials of the drug began in the summer of 1998, and the FDA approved the drug less than three months after the manufacturer applied to market it, after reviewing three separate studies of the drug involving over 1,000 patients.

"It’s important to realize that although the approval was fast, it is the culmination of years of work," says Health and Human Services (HHS) Secretary Tommy G. Thompson. HHS is the parent organization of the FDA.

The drug is expected to be on pharmacy shelves by the end of May.

Gleevec is a signal transduction inhibitor, meaning it interferes with an abnormal enzyme that sends signals to the nucleus of a cancer cell, telling that cell to multiply.

In early trials against CML, Brian J. Druker, MD, of Oregon Health Sciences University, who helped develop the drug, reported that Gleevec induced remission within weeks in almost all (98%) of 83 CML patients given 300 milligrams a day of the drug by mouth. In 12% of the patients, all signs of leukemia — even in the bone marrow — disappeared.

Studies showed it also worked in some patients with more advanced CML in a life-threatening phase called blast crisis — and in some patients with another form of leukemia, acute lymphocytic leukemia (ALL). The key to its working in all those patients was the presence of the Philadelphia Chromosome, a mutation (undesirable change) in a gene resulting in the production of the abnormal enzyme constantly signaling cells to grow and divide.

Some scientists caution that while the immediate benefits are obvious, it will take more time and study to know whether the drug means most CML patient will actually live longer.

Side effects were generally less severe than with more conventional cancer treatments, though some patients in trials reported some degree of nausea, vomiting, edema and other side effects.

Because tests showed other cancers were also influenced by the same class of enzymes, involved in CML, Druker and Finnish researchers decided to try it as well in a patient with a rare form of previously incurable stomach cancer known as gastrointesinal stromal tumor (GIST).

The drug shrank her tumor by more than half with minimal side effects, and put the patient into an extended remission. More information on the use of the drug in that cancer is expected to be released at the annual meeting of the American Society of Clinical Oncologists (ASCO) beginning Saturday in San Francisco, which will be covered here on the ACS web site.

Because other cancers besides leukemia and GIST are also influenced by the tyrosine kinase enzymes, trials with Gleevec are currently underway in patients with brain cancer. According to Novartis Pharmaceuticals, trials for one form of prostate cancer and small cell lung cancer have recently closed, and they are examining the results. Trials for GIST and brain cancer are still open for enrollment, however.

Several similar drugs — drugs that attack only abnormal cells or abnormal elements of cells — have begun to emerge from the laboratory in recent years after decades of research into the biological differences between cancer cells and normal cells. Use of the knowledge gained in that effort to design drugs that focus on those abnormalities is called rational drug design, and is seen by many as the currently emerging future reality of cancer treatment — of "kinder and gentler" cancer therapies.

"This drug targets only abnormal cells, and corrects the problem — an abnormal enzyme — that causes cancerous cells to grow out of control," says Ralph Vogler, MD, scientific program director for extramural grants of the American Cancer Society. "This is another example of the emerging importance of this new class of drugs — the ‘molecular target’ drugs."