1 INTRODUCTION
Gastrointestinal stromal tumors (GIST) are the most common type of
sarcoma derived from the digestive tract and are characterized by the
common presence of oncogenic mutations in genes encoding the KIT or
PDGFRA receptor tyrosine kinases.1 The advent of imatinib, a tyrosine
kinase inhibitor (TKI), has greatly improved the oncological outcomes of
GISTs. 1,2 It has been widely validated that the
patients with resected GIST at intermediate-, high-risk could benefit
from the imatinib adjuvant setting, especially recurrence-free survival
(RFS).3-13 A randomized clinical trial (SSG XVIII/AIO)
reported that RFS was significantly better in 3 years of imatinib when
compared with 1-year arm, indicating that prolonged the duration of
imatinib adjuvant therapy leading to improving the prognosis of these
patients.10 Furthermore, it has been reported that
about 50% of deaths may be avoided during the first 10 years of
follow-up following surgical resection with longer adjuvant imatinib
treatment.13
However, it is noted that approximately 50% of the patients
discontinued imatinib treatment early. Of these, quite a proportion of
patients are intolerant to imatinib-related adverse
reactions.10 In real clinical practice, physician
usually consider dose reduction for the above patients with GISTs to
alleviate drug toxic effects and the maintenance of imatinib treatment.14-18So far, the feasibility of low-dose imatinib
adjuvant therapy remains unknown. Generally, imatinib is initiated at a
fixed dose of 400mg/d in the patients regardless of body, which is
thought to be a potential contributor to variability in imatinib
systemic exposure.
On the other hand, numerous studies have shown that imatinib plasma
trough concentration (Cmin) is significantly associated
with the prognosis of GISTs and chronic myelogenous leukemia (CML).19-21Furthermore, the patients with a threshold of
Cmin ≥ 1100ng/mL have a favorable prognosis when
compared to those with Cmin less than
1100ng/mL.19 Another real-world study demonstrated
that the correlation of threshold of Cmin 760 ng/mL in
patients with prolonged progression-free survival
(PFS).20 Thus, it is necessary to underscore the
significance of close clinical monitoring to continue imatinib treatment
for patients at intermediate and high risk.
In this case, we conducted a retrospectively cross-sectional study, and
collected and analyzed data on patients with resected GIST treated in
our institute with imatinib at either 200 mg daily, 300 mg daily, 400 mg
daily, or 600 mg daily, to elucidate the impact of
different dosages of imatinib on
these patients. In addition, the distribution of the imatinib
Cmin at different levels of doses in patients was
evaluated in this study. Collectively, the main objective of this study
was to explore that imatinib Cmin, as a biomarker, is
used to evaluate the feasibility, safety, and efficacy of the different
levels of imatinib doses in the adjuvant treatment setting.