Resistance development during long-term treatment with Imatinib of patients with recurrent and/or metastatic gastrointestinal stromal tumors – single center experience

Aims: Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors of the gastrointestinal tract. They are supposed to arise from Cajal cells because of gain-of-function mutations of the tyrosine receptor kinases kit or PDGF-R. The small molecule Imatinib selectively inhibits the kinase activity of both receptors and has been used successfully in the treatment of GIST since 2001. However, increasingly resistance against Imatinib has been reported with a mean time to progression of 24 months. Here we report our experience in treatment of relapsed or metastasized GIST.

Patients: Fourteen consecutive patients with relapsed or metastasized GIST were treated with 400mg of Imatinib daily. Mean duration of treatment was 34,4 months. One patient had primary resistance and died two months after diagnosis. 3 patients developed progressive disease and died after a mean treatment time of 18 months in spite of increase of Imatinib dosages to 800mg daily. The remaining 10 patients had stable disease (2 patients) or partial response (8 patients) after a mean treatment time of 39.2 months. The first patient has been treated for 5 years. No further Imatinib resistance after prolonged treatment has been observed so far. No grade 3 or 4 side effects were observed.

Conclusions: From our single center experience resistance rates to Imatinib are below the rates given in the literature (50% within 2 years).