Purpose. This retrospective, nonrandomized study investigated the effect of imatinib rechallenge plus best supportive care (BSC) on overall survival after imatinib and sunitinib treatment for patients with locally advanced or metastatic gastrointestinal stromal tumor (GIST). Methods. Twenty-six patients who had previously been exposed to both imatinib and sunitinib were enrolled in this study. The treatment regimen was BSC with or without imatinib, based on the patient’s choice after discussion with his or her physician. The primary endpoint was overall survival, and secondary endpoints were time to treatment failure, clinical response rate assessed by Choi criteria, and safety. Results. Fourteen patients were treated with imatinib plus BSC and 12 received BSC alone. Median overall survival was greatly improved for the imatinib group, although differences were not significant (22 months for imatinib plus BSC versus 4 months for BSC; ). Three patients (21%) had a clinical response in the imatinib group, and one had a clinical response in the BSC alone group. Imatinib was well tolerated. Conclusions. Rechallenge with imatinib may be associated with improvement in overall survival without deteriorating performance status in patients who failed imatinib and sunitinib. A prospective study should be considered to confirm the efficacy of rechallenge with imatinib. 1. Introduction Gastrointestinal stromal tumor (GIST) is the most common type of nonepithelial tumor occurring in the gastrointestinal (GI) tract, including the peritoneum [1]. GISTs cannot always be distinguished from myogenic or neurogenic neoplasms by routine histological methods; as such, immunohistochemistry is often needed to distinguish GISTs from other spindle cell tumors. GISTs are generally considered to be KIT (CD117) positive tumors [2]. The tumor probably arises from KIT or platelet-derived growth factor receptor A (PDGFRA) gene mutations in precursor cells that normally give rise to the interstitial cells of Cajal [3–5]. Some GISTs are clinically malignant and metastasize predominantly to the liver and peritoneum [1, 6, 7]. About 85–90% of GISTs are associated with gain-of-function KIT gene mutations that lead to constitutive activation of KIT kinase activity [3]. A much smaller proportion of GISTs are associated with analogous gain-of-function mutations in PDGFRA, the gene-encoding platelet-derived growth factor receptor (PDGFR ); less than 10% contain no identified receptor tyrosine kinase mutations [8, 9]. Activating mutations of KIT or PDGFRA have been identified in the development
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