Phase II clinical trial of imatinib mesylate in therapy of KIT and/or PDGFRalpha-expressing Ewing sarcoma family of tumors and desmoplastic small round cell tumors

Abstract

Background: We have previously shown that the receptor tyrosine kinases, KIT and PDGFRalpha, 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 PDGFRalpha.

Patients and methods: Patients were selected for tumor immunohisto-chemical expression > or =2+/4+ for KIT or PDGFRalpha. 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+ PDGFRalpha 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 PDGFRalpha inhibitors are needed.