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Clinical Trial Results

Summaries of Newsworthy Clinical Trial Results < Back to Main
  • Posted: 03/14/2002
  • Reviewed: 12/20/2005

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Imatinib Mesylate (Gleevec™) Looks Even Better for Chronic Myelogenous Leukemia

Key Words: chemotherapy, chronic myelogenous leukemia, imatinib mesylate (Gleevec™). (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Patients with chronic myelogenous leukemia (CML) responded well to the molecularly targeted drug Gleevec (imatinib mesylate, also known as STI571) and experienced few severe side effects, researchers reported in the February 28, 2002, issue of the New England Journal of Medicine (see the journal abstract).

Gleevec was approved to treat CML in May 2001 on the basis of dramatically positive results in three short, early-phase clinical trials. The new phase II study offers evidence of the drug's effectiveness in a larger number of patients followed for a longer period of time.

The multicenter study involved 454 patients with CML that had not responded to therapy with interferon. All of the patients, whose average age was 57, took 400 mg of Gleevec daily. After an average of 18 months of follow-up, 95 percent of the patients were alive and an estimated 89 percent were free of disease progression.

"Gleevec represents a major advance in the treatment of CML," said Bruce D. Cheson, M.D., of the National Cancer Institute's Cancer Therapy Evaluation Program. The drug is a forerunner of a new generation of cancer treatments that will involve agents directed at specific immunologic or molecular targets, he said. "This targeted approach will, hopefully, increase our ability to cure patients with cancer."

However, no data from studies of Gleevec yet show whether the drug lengthens the lives of patients with CML, Cheson added. Additional trials that follow patients for a longer time are needed to determine whether Gleevec actually cures this disease. Studies of Gleevec in combination with other chemotherapy drugs are also called for.

In the recently reported study, 60 percent of patients taking Gleevec had a major cytogenetic response, or significant reduction in the number of cancerous cells. Within that subgroup, 69 percent experienced a complete cytogenetic response (disappearance of cancerous cells). These response rates are considerably higher than those observed in other studies in which patients were treated with interferon or other therapies, say the authors, who were led by Hagop Kantarjian, M.D., of the M. D. Anderson Cancer Center in Houston. Serious drug-related side effects, such as severe nausea, vomiting, fever and drops in platelet counts were seen in only six percent of patients.

Gleevec targets an abnormal version of a normal cellular protein that is present in nearly all CML patients. The abnormal protein is much more active than the normal version and is probably the cause of the disease. By blocking the abnormal protein, called BCR-ABL, Gleevec kills the leukemic cells. It is the first approved drug that directly turns off the signal of a protein known to cause a cancer. Unlike other drugs used in cancer treatment, Gleevec does not kill normal cells in addition to cancer cells.

CML is a disease in which too many white blood cells are made in the bone marrow, the spongy tissue inside large bones. Most of the 4,500 Americans diagnosed with CML each year are middle-aged or older, although the cancer can occur in children. In the first stages of CML, most people do not have any symptoms of cancer, and the disease progresses slowly.

Bone marrow transplantation in the initial phase of CML is the only known cure for the disease. However, the risk of death or serious side effects from transplantation increases with age. Many patients are not young or healthy enough to tolerate transplantation or do not have a suitable marrow donor.

Patients who did well on Gleevec tended to be those who had less advanced disease and who had previously responded to treatment with interferon, the researchers say. Other clinical trials are testing whether combining Gleevec with other drugs can improve response rates in patients with advanced CML.

A separate, large phase III trial is comparing the effectiveness of Gleevec with standard treatment, interferon plus low-dose cytarabine, in patients with newly diagnosed CML. In January, Gleevec's manufacturer, Novartis Pharmaceuticals, announced that an interim analysis of this trial had found a "substantially higher" response among patients treated with Gleevec. As a result, the trial protocol has been changed to enable patients who have not achieved a major cytogenetic response after one year of treatment with interferon and cytarabine to switch to Gleevec.

This trial, known as the International Randomized Study of Interferon vs. STI571 (IRIS) has enrolled 1,106 patients and is being conducted in 16 countries. Its results should help to determine whether Gleevec improves the long-term survival of patients with CML. Those interested in getting more information about Gleevec can call Novartis's patient assistance hotline at 1-877-GLEEVEC (1-877-453-3832).

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