George Daniel Demetri

Learn More
Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits KIT kinase activity. Here we show that approximately 35% (14 of 40) of GISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase,(More)
Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput(More)
PURPOSE Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients(More)
PURPOSE To assess potential differences in progression-free or overall survival when imatinib mesylate is administered to patients with incurable gastrointestinal stromal tumors (GIST) at a standard dose (400 mg daily) versus a high dose (400 mg twice daily). PATIENTS AND METHODS Patients with metastatic or surgically unresectable GIST were eligible for(More)
The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic(More)
BACKGROUND Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours (GIST), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression. We aimed to assess efficacy and safety of regorafenib in patients with metastatic or unresectable GIST(More)
PURPOSE Most gastrointestinal stromal tumors (GISTs) harbor mutant KIT or platelet-derived growth factor receptor alpha (PDGFRA) kinases, which are imatinib targets. Sunitinib, which targets KIT, PDGFRs, and several other kinases, has demonstrated efficacy in patients with GIST after they experience imatinib failure. We evaluated the impact of primary and(More)
BACKGROUND Gastrointestinal stromal tumour is the most common sarcoma of the intestinal tract. Imatinib mesylate is a small molecule that inhibits activation of the KIT and platelet-derived growth factor receptor alpha proteins, and is effective in first-line treatment of metastatic gastrointestinal stromal tumour. We postulated that adjuvant treatment with(More)
BACKGROUND Sunitinib, a multitargeted tyrosine-kinase inhibitor, which is approved by both US and European Commission regulatory agencies for clinical use, extends survival of patients with metastatic renal-cell carcinoma and gastrointestinal stromal tumours, but concerns have arisen about its cardiac safety. We therefore assessed the cardiovascular risk(More)
PURPOSE To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF). UPDATE METHODOLOGY The Update Committee completed a review and analysis of pertinent data published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated(More)