Wu Xingye, Ge Yinggang, He Xuemei, Li Juan, Zhang Jun
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Surg. 2023 Feb 23;10:1115141. doi: 10.3389/fsurg.2023.1115141. eCollection 2023.
Imatinib is the first-line adjuvant treatment for gastrointestinal stromal tumors (GISTs). Considering that some studies have suggested that imatinib (IM) plasma trough levels (C) change with time, the aim of this study is to assess the changes in IM C in patients with GIST in a long-term study and to elucidate the relationships between clinicopathological features and IM C.
In 204 patients with intermediate- or high-risk GIST who were taking IM, IM C was analyzed. Patient data were grouped according to the duration of medication (A: 1-3 months, B: 4-6 months, C: 7-9 months, D: 10-12 months, E: ≤12 months, F: 12<-≤36 months, G: >36 months). The correlation between IM C at different time stages and clinicopathological characteristics was assessed.
Statistically significant differences were observed between Groups A, C, and D ( = 0.049 and 0.01, respectively). In Group E, IM C correlated with sex ( = 0.049) and age ( = 0.029) and negatively correlated with body weight, height, and body surface area ( = 0.007, 0.002, and 0.001, respectively). In Groups F and G, IM C was significantly higher in non-gastric operation patients than in patients with gastrectomy ( = 0.002, 0.036) and was significantly higher in patients with the primary sites of others than in the stomach ( < 0.001, = 0.012). In addition, IM C was much higher in patients with mutation sites other than KIT exon 11 in Group F ( = 0.011).
This is the first study of IM C during the long-term treatment of patients with intermediate- or high-risk GIST. IM C was the highest for the first 3 months and then declined, and long-term administration of IM showed a relatively stable plasma trough level. The IM C correlated with different clinical characteristics at different durations of medication. This meant that future "trough level-clinicopathological characteristics" analyses should be time-point-specific. We also need to formulate time-specific medication monitoring plans in clinical practice to study disease progression caused by the occurrence of drug resistance.
伊马替尼是胃肠道间质瘤（GIST）的一线辅助治疗药物。鉴于一些研究表明伊马替尼（IM）的血浆谷浓度（C）会随时间变化，本研究旨在通过一项长期研究评估GIST患者IM C的变化，并阐明临床病理特征与IM C之间的关系。
对204例服用IM的中高危GIST患者的IM C进行分析。患者数据根据用药时长分组（A组：1 - 3个月，B组：4 - 6个月，C组：7 - 9个月，D组：10 - 12个月，E组：≤12个月，F组：12＜-≤36个月，G组：＞36个月）。评估不同时间阶段的IM C与临床病理特征之间的相关性。
在A组、C组和D组之间观察到具有统计学意义的差异（分别为 = 0.049和0.01）。在E组中，IM C与性别（ = 0.049）和年龄（ = 0.029）相关，与体重、身高和体表面积呈负相关（分别为 = 0.007、0.002和0.001）。在F组和G组中，非胃部手术患者的IM C显著高于胃切除患者（ = 0.002、0.036），原发部位为其他部位而非胃部的患者IM C显著更高（＜0.001， = 0.012）。此外，F组中KIT外显子11以外有突变位点的患者IM C更高（ = 0.011）。
这是首次对中高危GIST患者长期治疗期间的IM C进行研究。IM C在最初3个月最高，然后下降，长期服用IM显示血浆谷浓度相对稳定。IM C在不同用药时长与不同临床特征相关。这意味着未来的“谷浓度 - 临床病理特征”分析应针对特定时间点。我们还需要在临床实践中制定特定时间的用药监测计划，以研究耐药性发生导致的疾病进展情况。
