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Irinotecan and temozolomide for Ewing sarcoma: The Memorial Sloan‐Kettering experience
Author(s) -
Casey Denise A.,
Wexler Leonard H.,
Merchant Melinda S.,
Chou Alexander J.,
Merola Pamela R.,
Price Anita P.,
Meyers Paul A.
Publication year - 2009
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22206
Subject(s) - medicine , irinotecan , temozolomide , regimen , neutropenia , progressive disease , surgery , phases of clinical research , clinical trial , sarcoma , oncology , chemotherapy , cancer , colorectal cancer , pathology
Abstract Background 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. Procedure We conducted a retrospective chart review to identify patients with recurrent/progressive ES treated with irinotecan [20 mg/m 2 /day × 5(×2)] and temozolomide (100 mg/m 2 /day × 5) in our institution. The best response achieved, time to progression (TTP), and associated toxicities were recorded. Results 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). Conclusions 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. Pediatr Blood Cancer 2009;53:1029–1034. © 2009 Wiley‐Liss, Inc.