SU11248, a multi-targeted tyrosine kinase inhibitor, can overcome imatinib (IM) resistance caused by diverse genomic mechanisms in patients (pts) with metastatic gastrointestinal stromal tumor (GIST)

摘要: 3001 Background: Resistance to Imatinib mesylate (IM) following initial tumor regression and disease control in GIST is increasingly recognized as an unmet medical need. IM resistance can be correlated with the appearance of secondary mutations KIT or PDGFRA tyrosine kinases lesions refractory IM; activation alternative signaling pathways different structural biology new mutant contribute emergence IM-resistant clones. Methods: Phase I/II clinical trial SU11248 pts progressing GIST. Tumor biopsies were obtained define mutational status by dHPLC sequencing assays. Results: 98 progressive have been enrolled this ongoing study; response data available 48 genotype determined 41. The phase II regimen chosen was 50 mg orally once daily for 4 weeks, followed a 2 week period off drug each 6 wk cycle. therapy induced benefi...