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Efficacy and Tolerability of Imatinib Mesylate In Advanced Gastrointestinal Stromal Tumors

Issue: Vol.9, No.4 - October 2010

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  1. Dr Ehab Abdou
    Department of Radiation Oncology, Faculty of Medicine,
  2. Mohamed Gaafar

Background: IMATINIB MESYLATE is considered the standard of care for advanced or metastatic gastrointestinal stromal tumors (GIST). It acts through inhibiting the ACTIVATED KIT receptor tyrosine kinase which is critical in the pathogenesis of GIST.

Methods: In our study we retrospectively evaluated the activity of Imatinib in patients with advanced or metastatic gastrointestinal stromal tumor. We assessed response rate as
primary end point. Tolerance 2nd response rate, time to failure after responses and survival were the secondary end points.

Results: A total of 10 patients data were collected who had received 400 mg of Imatinib daily for advanced or metastatic GIST. Seven patients (70%) had a partial response while 3 patients (30%) had stable disease. No patient had a complete response.

The follow up period ranged between 5 month and 32 month with a median of 18 months.

Tolerance was acceptable and manageable where mild to moderate degree (Table 2). Eight patients had edema (80%), 7 patients had diarrhea (70%), 5 patients had nausea (50%) and 4 patients had fatigue (40%). Other side effects included myalgia or musculoskeletal pain (in 40 %), dermatitis or rash (in 30%), headache (in 30%), and abdominal pain (in 30%). Gastrointestinal hemorrhage (GIT Hge) recorded for one patient (10%). One patient discontinues the treatment for non-toxicity related reason.

On starting dose of Imatinib 400 mg, seven patients (70%) had partial response (PR) and 3 patients (30%) had stable disease (SD). While on re-challenging with higher dose 800 mg for progressive disease, 4 patients (40%) had PR and 3 patients (30%) had SD. None of patients had CR or PD when started either doses (table 2). All these responses were confirmed by repeated imaging at least 28 days later.

The minimal response duration was 3 months while the maximum was 21 months. The response median duration was 14 months after the onset of response. Seven patients had PD and challenged with 800 mg Imatinib daily dose and successfully maintained response for minimal 2 months and maximum 14 months with a median of second response to be 10.5 months.

Conclusions: In patients with an advanced unresectable or metastatic gastrointestinal stromal tumor, the objective response rate to Imatinib 400 mg is long lasting and can be repeated by higher doses i.e. 800 mg but with manageable higher rate of toxicity.

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