Phase II Clinical Trial of Imatinib Mesylate in Therapy of KIT and/or PDGFRα-expressing Ewing Sarcoma Family of Tumors and Desmoplastic Small Round Cell Tumors

Background: We have previously shown that the receptor tyrosine kinases, KIT and PDGFRα, are expressed on ESFT cell lines, and that imatinib induces dose-dependent apoptosis (1). We conducted a Phase II trial to evaluate the effectiveness of imatinib for patients with recurrent ESFT or DSRCT expressing KIT and/or PDGFRα. Patients and Methods: Patients were selected for tumor immunohisto- chemical expression ≥2+/4+ for KIT or PDGFRα. Imatinib was administered orally 400 mg twice/day for 28 days/course. Primary endpoint was response. Results: Seven patients were enrolled and evaluated. One patient with 3+/4+ PDGFRα and 3+/4+ KIT expression had a partial response through 8 courses. 4 patients had progression after 1 cycle. Two patients were not evaluable due to one early death and one refusing treatment. Conclusion: This study intended to enrich for molecular factors that potentially predict response. Given the poor prognosis with recurrent ESFT, further studies with other novel KIT and PDGFRα inhibitors are needed. The prognosis for long-term survival in non-metastatic Ewing sarcoma family of tumors (ESFT) has dramatically improved from <15% to 5-year EFS of 60-70% with the advent of multi-agent chemotherapy (2, 3). Despite this success, there remain patients who present with adverse prognostic factors