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Drug Works When Gleevec Fails Tumor Patients

   Portland, Ore.

OHSU Cancer Institute, VA Researcher Finds New Drug For Patients With Gleevec-Resistant Gastrointestinal Stromal Tumors

Oregon Health & Science University Cancer Institute and Portland Veterans Affairs Medical Center researcher, as well as scientists at several sites throughout the world, have found that a pill called Sutent (sunitinib) extends the lives of people with gastrointestinal stromal tumors (GIST) whose tumors are resistant to the only other available drug, Gleevec. The study was published online in the British journal The Lancet.

"Sutent made a huge difference. We know now that we have two drugs to treat GIST," said Michael Heinrich, M.D., a member of the OHSU Cancer Institute and a professor of medicine (hematology and medical oncology and cell and developmental biology) in the OHSU School of Medicine and the Portland VAMC.

In this clinical phase III study, Sutent was shown to be more active than a placebo. The median time to tumor progression (growth on X-ray study) was 27 weeks versus six weeks when patients were taking a placebo.

Between December 2003 and January 2005, 312 patients were enrolled in 11 countries and were randomized to receive blinded sunitinib or a placebo. Patients whose tumors progressed while they were taking the placebo were given the opportunity to switch to Sutent.

Each year, 5,000 to 10,000 Americans are stricken with GIST, which invades the organs or linings of the gastrointestinal tract. The standard of treatment for these patients has been with another oral medication, Gleevec, a drug originally developed at the OHSU Cancer Institute by Brian Druker, M.D., in collaboration with scientists at Novartis. Before Gleevec, there was no treatment except surgery, which was only feasible for patients with localized, early-stage disease.

Gleevec was the first drug to demonstrate that molecular targeted therapy works. Initially used to treat patients with chronic myelogenous leukemia, it has also proved successful in treating GIST. But Gleevec only helps about 80 percent to 85 percent of GIST patients, and even when it does work, many GIST patients may experience regrowth of their tumor. For the average patient, tumor regrowth is noted after 20 to 24 months of treatment. Sutent inhibits some of the same molecular targets as Gleevec. In addition, Sutent also has the ability to inhibit the function of the abnormal blood vessels that feed into tumors.

In January 2006 the U.S. Food and Drug Administration approved Sutent for the treatment of Gleevec-resistant GIST.

Just eight years ago there was no treatment for GIST patients. However, beginning in 2000, clinical study of Gleevec at the OHSU Cancer Institute and other centers around the world discovered the remarkable effectiveness of Gleevec for treating GIST patients.

"In eight years we've now been able to develop two drugs that are very effective and have fewer side effects than chemotherapy. If we continue to understand what's wrong with tumors, we can rapidly develop new treatments that can be used to give cancer patients a longer and better life," Heinrich said.

Next, he said, there is a need for studies to determine whether Gleevec or Sutent is the best therapy to use for the initial treatment of GIST. In addition, studies will be conducted to find out whether a combination of Gleevec and Sutent may be even more effective than either drug used alone. Sutent is marketed by Pfizer pharmaceutical company.

The principle investigator of this study is George Demetri, M.D. of the Dana Farber Cancer Institute, Boston, Mass. The senior author is Paulo G. Casali, M.D., of the Istituto Nazionale Tumori, Milan, Italy. Charles Blanke, M.D., co-leader of the OHSU Cancer Institute Solid Tumors Program, was the principle clinical investigator at OHSU Cancer Institute.

Particulars: Brian Druker, M.D., is JELD-WEN Chair of Leukemia Research at Oregon Health & Science University Cancer Institute and Investigator of Howard Hughes Medical Institute. He is an adjunct professor of medicine, division of hematology and medical oncology and has joint appointments in the department of cell and developmental biology and the department of biochemistry and molecular biology.

The OHSU Cancer Institute remains the only cancer center designated by the National Cancer Institute center between Sacramento and Seattle. It comprises some 120 clinical researchers, basic scientists and population scientists who work together to translate scientific discoveries into longer and better lives for Oregon's cancer patients. In the lab, basic scientists examine cancer cells and normal cells to uncover molecular abnormalities that cause the disease. This basic science informs more than 200 clinical trials conducted at the OHSU Cancer Institute.

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