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

Oregon Health & Science University Cancer Institute and Portland Veterans Affairs Medical Centre 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 tumours (GIST) whose tumours 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 (haematology 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 tumour 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 tumours 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 leukaemia, 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 tumour. For the average patient, tumour 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 tumours.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 centres 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 tumours, 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 Tumours Program, was the principle clinical investigator at OHSU Cancer Institute.(Source: The Lancet: Oregon Health & Science University Cancer Institute: October 2006.)