EMBARGOED FOR RELEASEUNTIL 12:45 p.m. PSTSATURDAY, DEC. 2, 2000
Kim Irwin ([email protected])(310) 206-2805Kambra McConnel [email protected])(310) 206-3769
NEW PILL FOR ADULT LEUKEMIA CONTINUES TO SHOW PROMISE IN EARLY TESTING, ACCORDING TO NEW DATA BEING RELEASED MONDAY AT THE AMERICAN SOCIETY OF HEMATOLOGY CONFERENCE
An experimental targeted therapy for chronic myelogenous leukemia (CML) continues to show promise in early testing, and it may help to battle the disease even at its most aggressive and deadly stage, according to a researcher at UCLA's Jonsson Cancer Center.
Dr. Charles Sawyers of UCLA's Jonsson Cancer Center studied the drug Glivec, formerly known as STI-571, in CML patients in myeloid blast crisis, the final stage of the disease that is usually fatal within four to six months. Sawyers is among several researchers presenting results from the second phase of clinical testing of the drug Monday (Dec. 4, 2000) at the annual meeting of the American Society of Hematology (ASH) in San Francisco.
Glivec, taken once a day in pill form, is being tested on more than 2,800 CML patients worldwide. Dramatic results from the first phase of testing, delivered at ASH last year, garnered national attention that had CML patients across the country clamoring to enroll in clinical trials.
At UCLA's Jonsson Cancer Center, more than 180 patients are enrolled in several clinical trials studying the effectiveness of the drug at various stages of CML. In the chronic stage, patients experience skyrocketing white blood cell counts, but generally don't exhibit symptoms for three to five years. The disease can advance to the accelerated stage, during which white blood cell counts increase even more. The end stage of the disease, known as blast crisis, often is fatal within several months. The results reported today by Sawyers indicate the drug can help patients in the final stage of CML. However, future studies will focus on pairing Glivec with other conventional cancer therapies, a combination that may prove more effective.
Worldwide, 260 patients in myeloid blast crisis were put on Glivec at 30 centers in six countries, said Sawyers, principal investigator for this CML study. The results are encouraging, Sawyers said, although patients in the final phase of the disease do not do as well on Glivec as those in the earlier stages of CML.
"The studies do show that this pill can produce dramatic remissions in patients with this rapidly fatal stage of leukemia," Sawyers said. "However, in the majority of patients, the remissions are short-lived. The next wave of studies will focus on Glivec in combination with other drugs. That's what we'll need to successfully treat blast crisis."
Researchers in Sawyers' lab at UCLA have discovered why the remissions are so short-lived, and will present their findings at the ASH meeting as well. Sawyers said the leukemia cells in blast crisis outsmart the drug by changing their gene expression. That information may help researchers find a more effective dose level of Glivec, or develop a targeted therapy to attack the new gene expression pattern, Sawyers said.
Glivec, developed by Novartis Oncology, attacks only cancer cells and leaves healthy cells alone. Such targeted therapies often result in few, if any, side effects for patients, Sawyers said.
Specifically, Glivec is a signal transduction inhibitor, a new class of drugs that can interfere with cell signaling pathways implicated in tumor development. Glivec is molecularly targeted to attack a mutant protein in a cancer-causing gene linked to CML, which strikes more than 10,000 adults worldwide every year. Much of the pioneering work linking the gene and its mutant protein with CML was done at UCLA's Jonsson Cancer Center by researcher Owen Witte, a professor of microbiology and a renowned investigator with the Howard Hughes Medical Institute. Sawyers, who did his postdoctoral training with Witte, participated in the research linking the mutant gene with CML.
Early testing of Glivec focused on patients in the chronic stage of the disease who did not respond to standard treatments with interferon. At doses of around 200 mg, nearly all the patients in the phase one studies had their white blood cell counts return to normal levels. At higher doses, the molecular cause of the disease -- the genetic mutation -- disappeared in some of the cases, Sawyers said.
The Phase II study results presented Monday by Sawyers focused on 260 patients in the myeloid blast crisis stage of CML. Of those, 64 percent had some kind of response to the drug, Sawyers said, including preliminary evidence of improved survival rates. Most patients in the blast crisis study received doses of 600 mg, Sawyers said.
In all, 50 abstracts based on data from ongoing studies of Glivec are being presented at the ASH meeting, which concludes Tuesday.
"We are extremely encouraged by the growing body of scientific evidence on our investigational agent Glivec and its potential role in treating certain forms of CML," said David Epstein, president of Novartis Oncology. "Novartis is committed to ongoing study of Glivec as a vital treatment option for physicians and patients in the battle against this disease."
Because of the encouraging results in early testing, Glivec may be submitted to the U.S. Food & Drug Administration for approval as soon as the first quarter of next year, according to a spokesperson for Novartis Oncology.
In the U.S. alone, more than 4,300 new cases of CML are diagnosed every year, according to the American Cancer Society. Of those cases, more than half will result in death. Because the chronic stage of the disease can last up to five years, the population of adults living with CML continues to increase, officials from the American Cancer Society said.
For more information about UCLA's Jonsson Cancer Center, call our clinical trials hotline at 888-798-0719. For more information about further testing of Glivec, call Novartis Oncology at 1-800-340-6843.
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For more information about UCLA's Jonsson Cancer Center, its people and resources, visit our site on the World Wide Web at www.cancer.mednet.ucla.edu
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