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.

BACKGROUND: Imatinib is the first-line adjuvant treatment for gastrointestinal stromal tumors (GISTs). Considering that some studies have suggested that imatinib (IM) plasma trough levels (Cmin ) change with time, the aim of this study is to assess the changes in IM Cmin in patients with GIST in a long-term study and to elucidate the relationships between clinicopathological features and IM Cmin .

METHODS: In 204 patients with intermediate- or high-risk GIST who were taking IM, IM Cmin 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 Cmin at different time stages and clinicopathological characteristics was assessed.

RESULTS: Statistically significant differences were observed between Groups A, C, and D ( P  = 0.049 and 0.01, respectively). In Group E, IM Cmin correlated with sex ( P  = 0.049) and age ( P  = 0.029) and negatively correlated with body weight, height, and body surface area ( P  = 0.007, 0.002, and 0.001, respectively). In Groups F and G, IM Cmin was significantly higher in non-gastric operation patients than in patients with gastrectomy ( P  = 0.002, 0.036) and was significantly higher in patients with the primary sites of others than in the stomach ( P  < 0.001, = 0.012). In addition, IM Cmin was much higher in patients with mutation sites other than KIT exon 11 in Group F ( P  = 0.011).

CONCLUSION: This is the first study of IM Cmin during the long-term treatment of patients with intermediate- or high-risk GIST. IM Cmin 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 Cmin 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.