Fractioned dose regimen of sunitinib for patients with gastrointestinal stromal tumor: a pharmacokinetic and treatment efficacy study.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
Yen-Yang
YY
Chen
GIST Team, Department of Surgery, Chang Gung Memorial Hospital, Linko, Chang Gung University, Taoyuan, Taiwan.
Chun-Nan
CN
Yeh
GIST Team, Department of Surgery, Chang Gung Memorial Hospital, Linko, Chang Gung University, Taoyuan, Taiwan.
Chi-Tung
CT
Cheng
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linko Medical Center, Taoyuan, Taiwan.
Chao-En
CE
Wu
Department of Surgery, Chang Gung Memorial Hospital-Keelung, Taiwan.
Kun-Chun
KC
Chiang
GIST Team, Department of Surgery, Chang Gung Memorial Hospital, Linko, Chang Gung University, Taoyuan, Taiwan.
Tsung-Wen
TW
Chen
Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
Chih-Chi
CC
Wang
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linko Medical Center, Taoyuan, Taiwan.
Jen-Shi
JS
Chen
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
Ta-Sen
TS
Yeh