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Back To Vidyya New England Journal Of Medicine Releases Phase I Data On Investigational Anti-Cancer Therapy - Glivec

NEJM Features Novel Agent's Activity In Chronic Myeloid Leukemia (CML) And Gastrointestinal Stromal Tumors (GIST)

The New England Journal of Medicine (NEJM) today published Phase I data regarding Glivec* [GLEE-vek] (formerly STI571), the oral investigational agent from Novartis Oncology for the treatment of patients with chronic myeloid leukemia (CML). Also featured in this issue of the NEJM is a case history of the treatment of a patient with a gastrointestinal stromal tumor (GIST). GISTs are solid tumors that express an activated protein shown to be inhibited by Glivec. The publication of these studies comes shortly after Novartis Oncology submitted applications with health authorities globally seeking marketing authorization for Glivec for the treatment of patients with chronic myeloid leukemia (CML) in blast crisis, accelerated phase or in chronic phase after failure of interferon-alpha therapy.

The applications are supported by data from three large Phase II studies of approximately 1,230 patients in 32 centers in five countries. To date, Glivec has been studied in more than 5,000 patients in 30 countries. Submissions have taken place in the United States, the European Union, Canada, Switzerland and Australia, with the application to be filed shortly in Japan.

Results Among CML Patients

NEJM cites that in the Phase I clinical trial evaluating Philadelphia chromosome-positive CML patients in chronic phase who were resistant or intolerant to interferon, 98 percent of these patients (53 of 54 total) achieved a complete hematologic response which has been maintained in 96 percent (51 of 53) of patients. A major cytogenetic response was found in 31 percent of patients (17 of 54 total), which thus far have been durable. Thirteen percent (7 of 54 total) of these patients had a complete cytogenetic response. A cytogenetic response indicates the disappearance or reduction of Philadelphia chromosome-positive cells. In the portion of this Phase I study evaluating Philadelphia chromosome-positive patients in myeloid blast crisis, 55 percent of patients (21 of 38 total) achieved a hematologic response (11 percent were complete responses). In the study arm evaluating Glivec in patients with acute lymphoblastic leukemia (ALL), 70 percent (14 of 20 total) achieved a hematologic response (20 percent were complete responses). Most of these patients began to relapse after 3 or 4 months.

Activity in GIST

Data from the case history featured in NEJM suggest that Glivec may have a role in patients with advanced, malignant GIST. The case history indicated that a considerable reduction in the patient's total tumor size, as assessed by positron emission tomography (PET)-scan images, was achieved within two weeks after treatment began. An objective, partial response, with 52 percent reduction in the total size of liver metastases, was achieved within one month after starting Glivec. At the time of publication of the data -- slightly more than one year after the first dose of Glivec -- all sites of tumor continued to respond to treatment.

As Glivec is still at an early phase of clinical testing for GIST, its safety and efficacy have not yet been established in this patient population, and clinical trial participants are being closely monitored.

About Glivec

Glivec represents a new type of antiproliferative agent called a signal transduction inhibitor (STI), which has been shown to have the potential to interfere with intracellular signaling pathways that have implications in tumor development. Glivec molecularly targets an abnormal protein produced by the specific chromosomal abnormality called the Philadelphia chromosome, which is present in a majority of patients with CML.

Glivec also has been shown to have the potential to target the c-kit protein tyrosine kinase receptor. This receptor is present, and in a majority of cases mutated, causing it to be continually active in GIST. Because Glivec demonstrated clinical activity in GIST, Novartis has expanded its trials to include inoperable or metastatic GISTs. These GIST trials are based on a collaborative, worldwide effort to treat more than 1,000 patients and will include clinical trials in conjunction with cancer cooperative groups in the United States, Canada, Europe, Australia, and potentially other organizations in Latin America and throughout the world.

Additionally, in programs of small-scale (proof-of-concept) studies, Novartis recently began investigating the role of Glivec in other solid tumors in which the biological mechanisms suggest potential activity for Glivec, including hormone refractory prostate cancer, gliomas (a cancer of the brain) and small-cell lung cancer. These pilot studies are intended to establish the basis for further investigations in clinical trials.

In clinical trials in CML, Glivec has been well tolerated with side effects including nausea, muscle cramps, edema, skin rash, diarrhea, heartburn and headache, which have been largely mild or moderate in intensity. Fewer than three percent of patients have experienced serious side effects such as the potential for liver toxicity, fluid retention and hemorrhages.

In the United States, patients and physicians interested in more information on these studies can contact the Novartis Oncology Clinical Trials Hotline at 1-800-340-6843, or the company's website, Patients outside the United States should contact the Medical Department of the local Novartis Pharma Company or consult the "contact us" section of the company's website,

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Editor: Susan K. Boyer, RN
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