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Mol Cancer Ther. 2018 Dec;17(12):2780-2787. doi: 10.1158/1535-7163.MCT-18-0498. Epub 2018 Oct 3.

Association of Imatinib Plasma Concentration and Single-nucleotide Polymorphisms with Adverse Drug Reactions in Patients with Gastrointestinal Stromal Tumors.

Zhang Q1,2, Xu J1,2, Qian Y3, Chen L4, Li Q1,2, Xu K1,2, Chen M1,2, Sun L3, He Z1,2, Yang L1,2, Zhang D1,2, Wang L1,2, Sun X5, Wang Y3, Xu H6,2, Xu Z6,2.

Author information

1
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
2
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
3
Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
4
Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
5
Department of Internal Medicine, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
6
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. hxu@njmu.edu.cn xuzekuan@njmu.edu.cn.

Abstract

Gastrointestinal stromal tumors (GIST) are the most prevalent mesenchymal tumors of the digestive tract. To investigate the association of imatinib mesylate plasma concentration with adverse drug reactions (ADRs) and influences of genetic polymorphisms on ADRs in GIST patients taking imatinib, a cohort of GIST patients consecutively treated with imatinib were included in the observational study. Clinical, pathologic and genotype information was recorded at enrollment and blood samples were collected at time as design. The plasma concentration of the imatinib was detected by LC-MS/MS. A questionnaire was used to evaluate the ADRs at each visit. SNPs in 13 genes were analyzed for a possible association with ADRs. The mean plasma trough concentration of 129 patients taking imatinib was 1.45 ± 0.79 μg/ml, average peak concentration was 2.63 ± 1.07 μg/ml. The imatinib concentration in patients treated with 600 mg/day was significantly higher than other dosage groups (P < 0.05). The ADRs were mostly mild. Edema, vomiting, and fatigue were significantly correlated with imatinib concentration (P < 0.05). Mutations of IL13 rs1800925 and CXCL14 rs7716492 were related with the incidence of leukopenia and rash in our research, separately (P < 0.05). We confirmed that with the increase of imatinib concentration, the incidence of edema, vomiting, and fatigue rises as well. Mutations of IL13 rs1800925 and CXCL14 rs7716492 may be the promising biomarkers to predict the ADRs of imatinib. The results of the study are of guiding significance for the use of imatinib in patients with GIST.

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