Application of therapeutic drug monitoring of imatinib for individual treatment of gastrointestinal stromal tumor

Koji Fukuda, Kazuhiro Shimazu, Taichi Yoshida, Masahiro Inoue, Masatomo Miura, Hiroyuki Shibata


Many molecular target agents are continuously administered at fixed dosages. Imatinib, which can control the growth of a gastrointestinal stromal tumor, is administrated at 400 mg/day. However, many patients cannot continue treatment because of adverse events, such as neutropenia. To obtain the best therapeutic response while maintaining quality of life, individualization should be considered. Study participants were gastrointestinal stromal tumor patients who required treatment with imatinib. Therapeutic drug monitoring was conducted using high-performance liquid chromatography. In our study, the trough (lowest) concentration that a drug reaches before the next dose is administered differed among patients. The grades of adverse events also differed individually. Moreover, the dosage that was necessary to shrink gastrointestinal stromal tumor differed in cases by cases. Dosage was modified according to the balance between blood concentration and therapeutic responses in order to minimize adverse events for individual patients, and to maximize the effect as the responses differed among patients. It was shown that based on therapeutic drug monitoring, individualization enabled the patients who may not normally continue the typical treatment to tolerate imatinib. According to the therapeutic drug monitoring, individualization of dosage of imatinib could improve the patients’ outcomes in both ends, therapeutic and adeverse responses.  


Therapeutic drug monitoring, Imatinib, Gastrointestinal stromal tumor

Full Text:



Ye ZK, Li C and Zhai SD. Guidelines for therapeutic drug monitoring of vancomycin: a systematic review. PLoS One. 2014; 9: e99044.

Deligiannidis KM, Byatt N and Freeman MP. Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. J Clin Psychopharmacol. 2014;34(2): 244-55.

Paci A, Veal G, Bardin C, et al. Review of therapeutic drug monitoring of anticancer drugs part 1--cytotoxics. Eur J Cancer. 2014;50(12): 2010-9.

Stotz M, Gerger A, Haybaeck J, et al. Molecular Targeted Therapies in Hepatocellular Carcinoma: Past, Present and Future. Anticancer Res. 2015;35(11): 5737-44.

Minguet J, Smith KH, Bramlage CP, et al. Targeted therapies for treatment of renal cell carcinoma: recent advances and future perspectives. Cancer Chemother Pharmacol. 2015;76(2): 219-33.

Miettinen M and Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med. 2006;130(10): 1466-78.

Lopes LF and Bacchi CE. Imatinib treatment for gastrointestinal stromal tumour (GIST). J Cell Mol Med. 2010;14(1-2): 42-50.

Bakhtiar R, Lohne J, Ramos L, et al. High-throughput quantification of the anti-leukemia drug STI571 (Gleevec) and its main metabolite (CGP 74588) in human plasma using liquid chromatography-tandem mass spectrometry. Analyt Technol Biomed Life Sci. 2002;768(2): 325-40.

Miura M, Takahashi N and Sawada K. Quantitative determination of imatinib in human plasma with high-performance liquid chromatography and ultraviolet detection. J Chromatogr Sci. 2011;49(5): 412-5.

Demetri GD, Wang Y, Wehrle E, et al. Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J Clin Oncol. 2009;27(19): 3141-7.

Yu H, Steeghs N, Nijenhuis CM, et al. Practical guidelines for therapeutic drug monitoring of anticancer tyrosine kinase inhibitors: focus on the pharmacokinetic targets. Clin Pharmacokinet. 2014;53(4): 305-25.

Klümpen HJ, Samer CF, Mathijssen RH, et al. Moving towards dose individualization of tyrosine kinase inhibitors. Cancer Treat Rev. 2011;37(4): 251-60.

Oostendorp RL, Buckle T, Beijnen JH, et al. The effect of P-gp (Mdr1a/1b), BCRP (Bcrp1) and P-gp/BCRP inhibitors on the in vivo absorption, distribution, metabolism and excretion of imatinib. Invest New Drugs. 2009;27(1): 31-40.

Noguchi K, Katayama K and Sugimoto Y. Human ABC transporter ABCG2/BCRP expression in chemoresistance: basic and clinical perspectives for molecular cancer therapeutics. Pharmgenomics Pers Med. 2014;7: 53-64.

Urquhart BL, Ware JA, Tirona RG, et al. Breast cancer resistance protein (ABCG2) and drug disposition: intestinal expression, polymorphisms and sulfasalazine as an in vivo probe. Pharmacogenet Genomics. 2008;18(5): 439-48.

Lee JH, Kim Y, Choi JW, et al. Correlation of imatinib resistance with the mutational status of KIT and PDGFRA genes in gastrointestinal stromal tumors: a meta-analysis. J Gastrointestin Liver Dis. 2013;22(4): 413-8.


Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.


International Journal of Cancer Therapy and Oncology (ISSN 2330-4049)

© International Journal of Cancer Therapy and Oncology (IJCTO)

To make sure that you can receive messages from us, please add the '' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.


Number of visits since October, 2013