The KIT tyrosine kinase inhibitor imatinib (IM) mesylate

The KIT tyrosine kinase inhibitor imatinib (IM) mesylate

has shown a promising clinical result for patients with advanced GIST [6], and several trials have shown a promising effect of this targeted therapy [6] and [7]. Our previous study showed that IM mesylate significantly affected survival in patients with GIST [8], [9] and [10]. However, progression of GIST eventually develops and emerges as a challenge. Sunitinib is a multitargeted tyrosine kinase inhibitor that predominantly targets vascular endothelial growth factor receptors and is used for treatment of metastatic renal cell carcinoma and GIST [11]. In addition to vascular endothelial growth factor receptors, sunitinib inhibits other receptor tyrosine kinases, including platelet-derived VX809 growth factor receptors ZVADFMK (PDGFRs), KIT, Fms-like tyrosine kinase-3, colony-stimulating factor 1, and RET, which are involved in a great variety of malignancies [12]. In GIST, sunitinib

is administered as a second-line targeted therapy, offering a new treatment option for patients who are refractory to IM. Although continuous once-daily dosing of sunitinib appears to be a safe and effective dosing regimen for patients with IM-resistant GIST, several adverse events (AEs), such as diarrhea, cutaneous toxicity, of hypertension, myelosuppression, and thyroid dysfunction, have been reported [12]. These drug-related toxicities may

reduce the treatment duration and patient compliance and therefore diminish treatment advantages of sunitinib. In this study, we investigated the efficacy, safety, and pharmacokinetics (PK) of administering the total daily dose of sunitinib in fractioned doses when treating GIST patients with IM intolerance or failure. The goal was to treat GIST patients with a regimen that has similar efficacy and a better safety profile. Between 2001 and March 2013, a total of 214 patients who had histologically confirmed, recurrent, or metastatic GIST that expressed CD117 or CD34 was treated at the Department of Medical Oncology and Surgery in Chang Gung Memorial Hospital in Taiwan. Failure of prior IM therapy, demonstrated by disease progression (based on Response Evaluation Criteria in Solid Tumors) [13] or discontinuation of IM due to toxicity, was one of the inclusion criteria in this study. Additional eligibility criteria included an Eastern Cooperative Oncology Group performance status of 0 or 1 and adequate cardiac, hepatic, renal, coagulation, and hematologic functions.

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