CLINICAL EXPERIENCE IN USING TARGETED THERAPY FOR DISSEMINATED GASTROINTESTINAL STROMAL TUMORS

We report a case of disseminated gastrointestinal stromal tumor effectively treated with imatinib, a selective tyrosine kinase inhibitor.

Background. Treatment of gastrointestinal stromal tumors (GIST ) still remains a clinical challenge. Since 2001 a breakthrough has occurred in the treatment of patients with GIST due to a successful use of imatinib, the targeted drug from the group of tyrosine kinase inhibitors, which is effective in the first line of inoperable and/or metastatic GIST , and is also used for neoadjuvant and adjuvant therapy for localized GIST . Genetic mutational analysis used for the correct prescription of targeted therapy suggests that it is inappropriate to administer imatinib in patients with a mutation in the succinate dehydrogenase gene and D842V mutation in the platelet-derived growth factor gene. However, in different regions of the Russian Federation, such diagnostic procedure may not always be available for a number of technical reasons. The lack of response to therapy and, consequently, the progression of the disease, may be associated with a decrease in the therapeutic concentration of imatinib in the blood plasma. Determination of the concentration of active metabolites of imatinib in the serum allows timely identification of potential causes of insufficient response to therapy and individual correction of the dose of the drug.

Material and Methods. To assess a significance of the correlation between increasing/decreasing the dose of imatinib and achieving a therapeutic response, we used a laboratory high-performance liquid chromatography method to determine the concentration of imatinib in serum.

Conclusion. Determination of a decreased concentration of active metabolites of imatinib in plasma by high-performance liquid chromatography with detection of tandem mass spectrometry method in a patient with disseminated GIST allowed us to correct the dose of the drug and achieve a positive effect with a duration of 51 months (since the dose was increased). The method of high-performance liquid chromatography with the detection of the method of tandem mass spectrometry is not an absolute alternative to gene mutation analysis, however, it can be effectively used for correction of the dose of imatinib in patients with GIST.

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