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AIM: Sunitinib has shown benefit in patients with imatinib (IM)–resistant gastrointestinal stromal tumor (GIST). However, its advantages are somewhat diminished because of associated toxicities. Herein, we clarify the efficacy and safety of fractioned dose regimen of sunitinib by a pharmacokinetic and efficacy study. MATERIALS AND METHODS: Between 2001 and March 2013, a total of 214 patients with metastatic GIST was treated at Chang Gung Memorial Hospital. Among them, 55 (11.6%) patients who received sunitinib were investigated. One group of patients was administered with standard dose of once-daily sunitinib (standard dose group) and the other group was administered with standard total daily dose of sunitinib in fractioned doses (fractioned dose group). RESULTS: Thirty-two male and 23 female patients with a median age of 55 years received sunitinib. The median duration of sunitinib administration was 9.2 months. The clinical benefit was 65.2%. The mean peak blood level of sunitinib in patients with fractioned doses was significantly lower than that in those with once-daily dose (83.4 vs 50.1 ng/ml, P = .01). The rates of adverse effects of hand-foot syndrome, mucositis, and yellow skin were significantly decreased by fractioned doses of sunitinib. However, the progression-free and overall survival did not differ between patients with different treatment regimens. CONCLUSION: The fractioned dose regimen of sunitinib appears to be a safe and effective treatment for patients with IM-resistant/intolerant GISTs. Significantly decreased toxicity of this regimen could be explained by significantly lower peak sunitinib blood level. However, the treatment efficacy is not reduced by this regimen.

PURPOSE: Our preliminary report of imatinib mesylate (IM) in gastrointestinal stromal tumor (GIST) patients detailed a high response rate; however, the long-term result is still unknown. We conducted an analysis of Taiwan advanced inoperable/metastatic GIST patients treated on IM regarding survival, pattern of failure, potential prognostic factors, and mutational status. PATIENTS AND METHODS: From 2001 to 2010, patients with pathologically proven advanced inoperable/metastatic GIST receiving IM were enrolled onto this study. Data on KIT mutational status, measurable tumor size, and other potential prognostic factors were prospectively collected. Patients were followed up for a median of 33.6 months. RESULTS: There were 171 patients (106 men and 65 women) with response rate, and their clinical benefit for IM was 57.3% and 87.1%, respectively. Median progression-free survival (PFS) and overall survival (OS) for these 171 patients are 37.6 and 71.0 months, respectively. Of 171 patients, 120 (70.2%) remained on long-term IM use. Poor performance status, tumor larger than 11.5 cm, primary resistance, and the presence of an exon 9 mutation were independently associated with unfavorable PFS. Regarding OS, poor performance status, primary resistance, and tumor larger than 11.5 cm were three independently unfavorable predictors. CONCLUSIONS: The median PFS and OS of 171 GIST patients are 37.6 and 71.0 months, respectively. Poor performance status, tumor size larger than 11.5 cm, primary resistance, and an exon 9 mutation were independently associated with unfavorable PFS. Regarding OS, poor performance status, primary resistance, and tumor size larger than 11.5 cm were three independent unfavorable predictors.