GIST SymposiumClinical management of gastrointestinal stromal tumors: Before and after STI-571*,**,*
Section snippets
Primary disease
The exact incidence of GIST in the United States is unknown at this time, because until very recently many of these cases were considered benign neoplasms or leiomyosarcoma. However, the estimated incidence of GIST is at least 1,000 new cases per year, and the actual incidence is probably much higher if very small (<1 cm) lesions found incidentally during laparotomy for other reasons are included. The awareness of GIST has increased because of the routine use of CD117 immunohistochemical
Development of STI-571
The application of STI-571 represents a major paradigm shift in cancer therapy—targeting the specific molecular abnormalities crucial in the etiology of cancer. In contrast, most anticancer therapies developed over the past 50 years have been essentially nonspecific. Cytotoxic agents generally function by interfering with cell machinery common to both neoplastic and normal cells (e.g., DNA synthesis). Consequently, conventional chemotherapeutic agents lack selectivity, have a narrow therapeutic
Correlative studies
The advent of STI-571 has revolutionized the clinical management of patients with primary and metastatic GIST, but our understanding of the genetic aberrations in GIST is just beginning to evolve. The 2 fundamental correlative questions regarding STI-571 use are (1) whether the type of c-kit mutation predicts sensitivity to STI571 and (2) what biologic mechanisms mediate tumor resistance to the agent
Current use of STI-571 and future considerations
STI-571 has quickly become the first-line agent for metastatic GIST. Patients who respond may become candidates for surgical resection. Patients with stable disease may remain on the agent until disease progression becomes evident. Patients who become refractory to STI-571 are eligible for more traditional palliative therapy, such as hepatic artery embolization, radiation, or surgical debulking and/or intraperitoneal chemotherapy. The combination of STI-571 and conventional therapeutic
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Cited by (0)
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Based on presentations given at the National Institutes of Health Workshop on Gastrointestinal Stromal Tumors, Bethesda, MD, April 2 and 3, 2001.
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Supported in part by the Northwest Health Foundation (M.H.), VA Merit Review program (M.H.), and National Cancer Institute (grant CA94503) (R.D.).
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Address correspondence and reprint requests to Ronald P. DeMatteo, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.