title: [A Chinese multi-center study on the significance of monitoring imatinib plasma concentration in patients with gastrointestinal stromal tumor before and after administration].
abstract: OBJECTIVE
  To investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.
  
  
  METHODS
  A cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.
  
  
  RESULTS
  Patients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R2=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R2=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R2=0.076, P=0.033).
  
  
  CONCLUSIONS
  The imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of General Surgery, The Affiliated Hospital of Nantong University, Nantong 226019, China.
authors.forename: Lilin
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of General Surgery, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Nanjing Drum Tower Hospital, Nanjing 210008, China.
authors.forename: Wenxian
authors.initials: W
authors.lastname: Guan
authors.affiliation: Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical Universityspital, Nanjing 210011, China.
authors.forename: Baolin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Jinling Hospital, Nanjing 210002, China.
authors.forename: Guoli
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of General Surgery, the Second People's Hospital of Lianyungang, Lianyungang 222006, China.
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of General Surgery, Shandong Provincial Hospital, Jinan 250021, China.
authors.forename: Leping
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of General Surgery, Jiangsu Province Tumor Hospital, Nanjing 210009, China.
authors.forename: Huanqiu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Zhejiang University, Hangzhou 310003, China.
authors.forename: Jiren
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Luning
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Diancai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Affiliated Hospital of Nantong University, Nantong 226019, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhi
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jianghao
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. xuzekuan@njmu.edu.cn.
authors.forename: Zekuan
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001549:Benzamides; D003131:Combined Modality Therapy; D003430:Cross-Sectional Studies; D005260:Female; D005743:Gastrectomy; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D011743:Pyrimidines; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate