AUTHOR=Wu Xingye , Ge Yinggang , He Xuemei , Li Juan , Zhang Jun 

TITLE=Changes in imatinib plasma trough level during long-term treatment in patients with intermediate- or high-risk gastrointestinal stromal tumors: Relationship between covariates and imatinib plasma trough level

JOURNAL=Frontiers in Surgery

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/surgery/articles/10.3389/fsurg.2023.1115141

DOI=10.3389/fsurg.2023.1115141

ISSN=2296-875X

ABSTRACT=<sec><title>Background</title><p>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<sub>min</sub>) change with time, the aim of this study is to assess the changes in IM C<sub>min</sub> in patients with GIST in a long-term study and to elucidate the relationships between clinicopathological features and IM C<sub>min</sub>.</p></sec><sec><title>Methods</title><p>In 204 patients with intermediate- or high-risk GIST who were taking IM, IM C<sub>min</sub> 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&lt;–≤36 months, G: &gt;36 months). The correlation between IM C<sub>min</sub> at different time stages and clinicopathological characteristics was assessed.</p></sec><sec><title>Results</title><p>Statistically significant differences were observed between Groups A, C, and D (<italic>P</italic> = 0.049 and 0.01, respectively). In Group E, IM C<sub>min</sub> correlated with sex (<italic>P</italic> = 0.049) and age (<italic>P</italic> = 0.029) and negatively correlated with body weight, height, and body surface area (<italic>P</italic> = 0.007, 0.002, and 0.001, respectively). In Groups F and G, IM C<sub>min</sub> was significantly higher in non-gastric operation patients than in patients with gastrectomy (<italic>P</italic> = 0.002, 0.036) and was significantly higher in patients with the primary sites of others than in the stomach (<italic>P</italic> &lt; 0.001, = 0.012). In addition, IM C<sub>min</sub> was much higher in patients with mutation sites other than KIT exon 11 in Group F (<italic>P</italic> = 0.011).</p></sec><sec><title>Conclusion</title><p>This is the first study of IM C<sub>min</sub> during the long-term treatment of patients with intermediate- or high-risk GIST. IM C<sub>min</sub> 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<sub>min</sub> 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.</p></sec>