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.