4 DISCUSSION
It is widely acknowledged that measuring the steady-state imatinib
Cmin level of imatinib is of important guiding
significance for medication instructions and dosage individualization
for GIST patients.14-17,19,20 The study conducted by
Demetri and colleagues found out that patients with advanced GIST with
the threshold of imatinib Cmin more than 1100 ng/mL have
a favorable progression-free survival (PFS) compared to these less than
1100 ng/mL.19 In this study, the imatinib
Cmin in 51.4 % of patients with GIST was more than
1,100 ng/mL. This outcome is superior to a study in Holland, where only
33.3% of patients had imatinib Cmin values of 1,000
mg/L in all samples of 180
patients.26Additionally, Bouchet et al found a significant correlation between the
imatinib Cmin threshold of 760 ng/mL and longer PFS for
patients with advanced GIST.20An increasing number of studies have demonstrated that imatinib
increases the RFS of GIST patients, while retaining patients on therapy
following a radical resection remains challenging because of
discontinuation of imatinib therapy occurring in a percentage of
patients owing to drug-related adverse events
(AEs).10,16 In addition, the study conducted by
Chandrajit P and colleagues reported that women were prone to
discontinuation of fixed-dose imatinib of 400mg/d, and had higher
imatinib Cmin levels compared with men, indicating that
lower doses could be considered. 9Although the
Cmin level of imatinib is associated with the prognosis
of GIST, it is still undefined that whether individualized dosage
adjustments based on the Cmin level would provide
clinical benefits to GIST patients, such as improving the long-term
prognosis and reducing imatinib-related toxicity. Additionally, the
findings of our study show patients in low-dose arms usually are
characterized by elderly female predominance and lower BSA. This is
consistent with the research conducted by Yuichi et
al.17 Moreover, no significant differences in RFS and
Cmin levels of 300- and 400-mg daily groups were
observed in our study, suggesting that it may be feasible to apply
individualized dosage adjustments based on the imatinib
Cmin level. On the other hand, numerous studies have
been shown that higher imatinib Cmin levels are
associated with imatinib-related toxicity.14,16,18 But
pharmacokinetic data were too limited to draw any significant
correlation of Cmin with drug toxicity in this study. It
is noteworthy that the Chinese and Japanese populations were prone to
experience imatinib treatment-related serious adverse events compared
with that in the population of European ancestry when with standard dose
of imatinib is 400 mg once daily.17,26,27
There are still several shortcomings
in this study, the mutation information of patients was limited because
of economic status and their wills. Therefore, we cannot further
investigate the impact of tumor mutational status on long-term
oncological outcomes of resected GIST patients with imatinib adjuvant
therapy. However, a multi-institutional European retrospective study
conducted by Bruno et al found that a daily dose of 800 mg versus 400mg
for GIST patients with harboring exon 9 kit mutations did not
demonstrate better outcomes in terms of survival results in the
post-operative setting, in agreement with the result of a study
conducted by Almudena and colleagues.12 In addition,
the result of the ACOSOG Z9001 trial shows that tumor genotype seems did
not have a significant impact on the RFS of resected patients at high
risk.5 Besides, the sample of our study was small, and
large sample, prospective multicenter research is warranted.
Furthermore, it is mandatory to establish the effective threshold of
imatinib Cmin of the Chinese population of GIST
patients.