[Sunitinib as a second-line therapy for imatinib-resistant gastrointestinal stromal tumors]

Gastrointestinal stromal tumor(GIST)is one ofthe representative diseases for which molecularly targeted therapy is very effective. Imatinib mesylate, a tyrosine kinase inhibitor of KIT and platelet-derived growth factor receptor(PDGFR), has dramatically improved the prognosis ofpatients with advanced, recurrent, and/or metastatic GISTs. Although the rate of response to imatinib therapy is high, the emergence ofimatinib -resistant tumors and the second-line therapy following imatinib therapy have become new clinical problems. Sunitinib malate, a multi-targeted tyrosine kinase inhibitor that shows activity against KIT and other receptor tyrosine kinases, including PDGFR and vascular endothelial growth factor receptor, is the only treatment for imatinib-resistant GISTs that is covered by national health insurance in Japan as ofthis writing. Several clinical trials that evaluated sunitinib as potential second-line therapy in Western countries and Japan found a clinical benefit rate of2 4 to 39% and a median time to progression of7 months. However, it is necessary to adequately manage the adverse events of sunitinib therapy in order to receive the full benefits of the therapy, because various severe adverse events, particularly thrombocytopenia and hand-foot syndrome in Japanese GIST patients, frequently lead to poor tolerability. Further investigation is required to find an appropriate regimen for Japanese GIST patients.