June 6, 2004

A new drug called SU11248 shrinks or slows the progression of cancer in patients with gastrointestinal stromal tumor (GIST) whose tumors have stopped responding to the standard treatment of imatinib (Gleevec). GIST is a rare cancer of the stomach or intestinal tract that is treatable with imatinib. However, imatinib eventually stops working in about half of all patients, and the cancer progresses.

"We're not replacing imatinib as initial therapy for GIST, but we need to develop better therapies and make their effects last longer," said lead author George D. Demetri, MD, Director, Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School in Boston, Mass.

In this small study, 48 patients with imatinib-resistant GIST were given SU11248 (taken as a pill once a day). Tumors in 26 patients (54%) either responded to this treatment or did not progress for six months or more. Tumors in six of the patients (13%) showed a partial response. The researchers also analyzed genes from the tumor samples and found that certain mutations, or changes, in a gene called KIT were associated with responses to SU11248. These studies are important because they may help researchers understand how this new drug works.

Researchers think that SU11248 blocks several enzymes, called kinases, which are believed to be involved in cancer cell growth. "There is evidence that SU11248 shuts down several switches in cancer cells, while imatinib only shuts down a few," said Dr. Demetri. "It may be possible that several switches need to be shut off in order for a patient to derive the most clinical benefit."

Although GIST is a rare cancer, the pathways involved in the development and spread of this cancer are similar to those in other cancers. "Studies of SU11248 in GIST give us the foothold in the door of cancer," said Dr. Demetri. He believes that knowing how this drug works could be helpful in understanding some of the more common cancers.

What This Means For Patients

This trial for GIST was a combination phase I/II trial, so results still need to be verified in a phase III trial. Until that research is complete, this drug is only available through clinical trials. For patients with GIST who are developing resistance to imatinib, these results indicate that SU11248 may delay the progression of this cancer in some patients. Finally, because many cancers have similar pathways to GIST, this drug might also be used to treat or understand other types of cancer.