Irinotecan and Temozolomide for Ewing Sarcoma: The Memorial Sloan-Kettering Experience

Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Pediatric Blood & Cancer (Impact Factor: 2.56). 12/2009; 53(6):1029-34. DOI: 10.1002/pbc.22206
Source: PubMed

ABSTRACT The prognosis for recurrent/progressive Ewing sarcoma (ES) remains poor. Pre-clinical, adult phase I and II trials have demonstrated the combination of irinotecan and temozolomide to have schedule-dependent synergy and significant antitumor activity. A pediatric phase I trial has shown this regimen to be safe and active in advanced ES.
We conducted a retrospective chart review to identify patients with recurrent/progressive ES treated with irinotecan [20 mg/m(2)/day x 5(x2)] and temozolomide (100 mg/m(2)/day x 5) in our institution. The best response achieved, time to progression (TTP), and associated toxicities were recorded.
Twenty patients received a total of 154 cycles of therapy. Of 19 evaluable patients, there were 5 complete and 7 partial responses (a 63% overall objective response). Median TTP for 20 evaluable patients with recurrent/progressive ES was 8.3 months; for the subset of 14 patients with recurrent ES, it was 16.2 months. Median TTP was better for patients who sustained a 2-year first remission than for those who relapsed < 24 months from diagnosis and for patients with primary localized vs. metastatic disease. Significant toxicities included grade 3 diarrhea (7 cycles), grade 3 colitis (1 cycle), grade 3 pneumonitis in one patient receiving concurrent whole-lung RT, grade 3-4 neutropenia (19 cycles), and grade 3-4 thrombocytopenia (16 cycles).
Irinotecan and temozolomide is a well-tolerated and active regimen for recurrent/progressive ES. Prospective trials are necessary to define the role of this regimen in newly diagnosed ES.

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