Targeted Treatment Developed For Leukemia Also Works For Intestinal Tumor, OHSU Study Finds

05/14/00    SAN FRANCISCO, Calif.

Molecular cause of gastrointestinal stromal tumors inhibited by STI571

More than half of patients with a fatal, chemotherapy-resistance form of cancer called gastrointestinal stromal tumors (GIST) have gone into remission on Gleevec (formerly called STI 571), the recently approved "leukemia pill." Results of the study are being presented today, Monday, May 14, by Charles Blanke, M.D., director of gastrointestinal oncology at Oregon Health & Science University's Oregon Cancer Institute, at the American Society of Clinical Oncology meeting in San Francisco.

The results show that 59 percent of the GIST patients went into remission after taking Gleevec. Also, 90 percent of patients in the study reported major signs of clinical improvement, including going off of pain-relieving narcotics, returning to work and resuming activities they had been unable to participate in.

"This is exciting news, not just because these results validate the theory of targeted therapy, but because these patients have no other options," said Blanke, associate professor of medicine (hematology and medical oncology), OHSU School of Medicine, and co-investigator of the multicenter study. "Not only are we seeing shrinkage in size and quantity of tumors, but patients are feeling better than they have in many months."

GIST affects about 5,000 - 10,000 Americans a year, striking any of the organs in the entire length of the gastrointestinal tract or its lining. These tumors are prone to spread to other organs and, once spread, they often are unresponsive to chemotherapy or irradiation and invariably fatal. Clinical trials for GIST using Gleevec began in July 2000 at OHSU, Dana-Farber Cancer Institute in Boston, Fox Chase Cancer Center in Philadelphia and Helsinki University Central Hospital in Finland.

Gleevec was considered a possible therapy for GIST after researchers identified the culprit protein KIT, which appears to drive the growth of intestinal tumors and is present in many GIST patients. Study results also show that patients expressing only the normal KIT protein before it begins to mutate have a 78 percent remission rate taking Gleevec. KIT is a tyrosine kinase similar in structure to BCR-ABL, the protein originally targeted by Gleevec. BCR-ABL is responsible for uncontrolled growth of white blood cells in CML. Gleevec has undergone safety trials in humans for CML and has produced dramatic results for patients in all phases of that disease.

"These results on GIST patients further confirm the idea of molecularly targeted therapy for cancer and prove it can also work with solid tumors when we know the target," said Brian Druker, M.D., director of the Leukemia Center at OHSU and co-developer of Gleevec. "When we developed this compound (in conjunction with Novartis Pharmaceuticals), we knew it was specific enough to have limited toxicity but also might target more than one protein."

In 1993 while studying the effects of Gleevec on cells, Druker found that the compound also inhibited KIT. Further research by Michael Heinrich, M.D., associate professor of medicine in the OHSU School of Medicine, and biologists at Dana-Farber confirmed the target and traced the specific activity of KIT in GIST cells.

Gleevec was approved by the FDA for chronic- and acute-phase CML treatment on Thursday, May 10. Gleevec is being tested on glioblastoma, a deadly brain cancer that is driven by a similarly structured protein.

Patients seeking more information about the CML or GIST clinical trials can call 503 494-1080 or visit