Irinotecan and temozolomide for Ewing sarcoma: the Memorial Sloan-Kettering experience.
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.


METHODS
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.


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.
Casey
Denise A
DA
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Wexler
Leonard H
LH
Merchant
Melinda S
MS
Chou
Alexander J
AJ
Merola
Pamela R
PR
Price
Anita P
AP
Meyers
Paul A
PA
D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D003092:Colitis / Q000139:chemically induced; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D011014:Pneumonia / Q000139:chemically induced; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000150:complications / Q000188:drug therapy*; D000077204:Temozolomide; D013921:Thrombocytopenia / Q000139:chemically induced; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide