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New Drug Shows Promise in Fight Against Chronic Myelogenous Leukemia An experimental drug called STI-571 has been remarkably effective in treating persons with chronic myelogenous leukemia (CML), reported researchers at the December 1999 meeting of the American Society of Hematology. Brian Druker, M.D., and colleagues at the Oregon Health Science University, M.D. Anderson Cancer Center, and the University of California at Los Angeles treated 61 patients with varying dosages the drug. All patients were in the chronic phase of CML and were resistant to interferon therapy. Those who took daily oral doses of at least 140 milligrams of STI 571 for four weeks had a 50-percent reduction in their white blood cell count. All 31 patients treated with dosages of 300 milligrams or more achieved normal white blood cell and platelet counts for up to eight months. Forty-five percent of the 31 had cytogenetic responses, three of which were complete (the chromosomal abnormality that caused the disease was eliminated), after two months of treatment. A second pilot study tested the effectiveness of STI 571 in treating 12 CML patients in blast crisis (an advanced stage of CML) and 10 patients with acute lymphocytic leukemia (ALL) who were Philadelphia chromosome positive. Although most patients achieved at least a partial remission of their disease, the remission was short-term. “This drug is probably as close to the true magic bullet as any drug in oncology has ever been,” says Hillard Lazarus, M.D, Professor of Medicine at Case Western Reserve University, and chairman of the Blood & Marrow Transplant Committee of the Eastern Cooperative Oncology Group. “Although testing is still in the early stages, the data I’ve seen suggest that STI 571 could be curative for a number of patients, or at least control the disease for a very long time without significant side effects.” Approximately 5,000 adults in the U.S. are diagnosed with CML each year. Abnormal stem cells in the bone marrow, created by an exchange of parts between two chromosomes (9 and 22), produce a protein called bcr-abl that stimulates the production of too many white blood cells. “It’s like leaving a switch in the on position,” says Lazarus. The white blood cells flood into the bloodstream, and often invade other tissues and organs. The current treatment of choice for persons with CML is an allogeneic bone marrow transplant. However, many people diagnosed with CML are either too old for an allogeneic transplant or do not have a suitable marrow donor. Those who are ineligible for a transplant are usually treated with injections of interferon. Although interferon can prolong survival, it seldom cures patients of their disease. Over time, CML becomes resistant to interferon, and many patients experience significant side effects such as fever, chills, fatigue, low blood counts, nausea, vomiting, diarrhea, loss of appetite, liver dysfunction, rash and nerve injury. STI 571 works by blocking the activity of the bcr-abl protein, thus “turning off the switch” on excessive white blood cell production. Side effects of STI 571 have been minimal—mild to moderate nausea, muscle cramps, heartburn and headache. Unlike interferon, STI 571 is taken orally rather than by injection. Novartis Pharmaceuticals Corporation, which manufactures STI 571, will continue testing the drug in a Phase II clinical trial this year. Approximately 20 medical centers in the U.S. and Europe will participate in the trial, says Gloria Stone, spokeswoman for Novartis. The trial will be open to patients with CML in the accelerated phase or blast crisis, as well as patients in the chronic phase whose disease is resistant to interferon or who are intolerant of interferon. Patients must be 18 years of age or older “These are baseline criteria for inclusion in the trial,” notes Stone. “The clinical investigator will have to more fully evaluate each patient to determine final eligibility.” The company will open a trial for pediatric patients in early 2000. In addition, a trial is planned to evaluate the effectiveness of combining STI 571 with chemotherapy to treat CML patients in blast crisis, and ALL patients who are Philadelphia chromosome positive. To learn more about the STI 571 clinical trials, U.S. residents should phone the Novartis Oncology Clinical Trials Hot Line at 800-340-6843. Persons outside the U.S. should contact the Medical Department of the local Novartis Pharma Company, or consult the “contact us” section of www.pharma.novartis.com—the company’s Website. |
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