Toxic effects were recorded in accordance with the National Cancer Institute Common Toxicity Criteria [14]. Blood samples were collected from selected patients in the study for PK analysis of sunitinib. The blood samples were collected 5 to 6 hours after drug administration to measure the peak levels of sunitinib. http://www.selleckchem.com/products/BIBW2992.html Each 8-ml blood sample was collected into heparinized polypropylene tubes, centrifuged at 1000g for 10 minutes for plasma

separation, and stored at below − 20 °C until analysis. Plasma concentrations of sunitinib and CGP74588 were determined by using a validated liquid chromatography–tandem mass spectrometry assay. The lower limit of quantification was 4 ng/ml for both sunitinib and CGP74588. Sections were prepared from formalin-fixed, paraffin-embedded, pretreated specimens that were trimmed to enrich tumor cells. Polymerase chain reaction amplification of genomic DNA for KIT and PDGFRA was performed and amplification was Panobinostat clinical trial analyzed for mutations as previously described [15]. All data are

presented as percentages of patients or means with SDs. Pearson Chi-square test and Fisher exact test were used for nominal variables. Survival rates were calculated and plotted with the Kaplan-Meier method and compared between groups with a log-rank test. All statistical analyses were performed using the SPSS computer software package (version 10.0; SPSS, Chicago, IL). A P value of less than .05 was considered to be statistically significant. Table 1 Tryptophan synthase summarizes the demographic features of 55 GIST patients who received sunitinib during the study period. There were 32 male and 23 female patients with a median age of 55 years old (ranging from 15 to 88 years). The stomach was the most common site for GISTs treated with sunitinib (23 patients; 35%), followed by the jejunum and ileum (15 patients; 22%), duodenum (4 patients), and the colorectum (6 patients; 13%; Table 1). The peak plasma level of sunitinib of patients in the standard dose group was significantly

higher than that of patients in the fractioned dose group (mean, 83.4 vs 50.1 ng/ml; P = .01; Table 2). Table 3 listed hematologic and non-hematologic AEs between two groups of patients. Generally, fractioned doses of sunitinib caused similar or relatively lower rates of AEs when compared with standard doses of sunitinib. In addition, the patients who received fractioned doses of sunitinib developed significant lower rates of yellow skin discoloration, grade 3/4 hand-foot skin reaction (HFSR), and mucositis when compared with those who received standard doses of sunitinib. In the standard dose group, the most common treatment-related non-hematologic AEs were HFSR (65%), hypertension (54%), diarrhea (42%), and mucositis (38%).