Casey Denise A, Wexler Leonard H, Merchant Melinda S, Chou Alexander J, Merola Pamela R, Price Anita P, Meyers Paul A
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Pediatr Blood Cancer. 2009 Dec;53(6):1029-34. doi: 10.1002/pbc.22206.
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.
复发性/进展性尤因肉瘤（ES）的预后仍然很差。临床前、成人I期和II期试验已证明伊立替康和替莫唑胺联合使用具有剂量依赖性协同作用和显著的抗肿瘤活性。一项儿科I期试验表明该方案在晚期ES中安全且有效。
我们进行了一项回顾性病历审查，以确定在我们机构接受伊立替康[20mg/m²/天×5（×2）]和替莫唑胺（100mg/m²/天×5）治疗的复发性/进展性ES患者。记录达到的最佳缓解、进展时间（TTP）和相关毒性。
20名患者共接受了154个周期的治疗。在19名可评估患者中，有5例完全缓解和7例部分缓解（总体客观缓解率为63%）。20例复发性/进展性ES可评估患者的中位TTP为8.3个月；14例复发性ES患者亚组的中位TTP为16.2个月。首次缓解持续2年的患者的中位TTP优于诊断后<24个月复发的患者以及原发性局限性疾病与转移性疾病患者。显著毒性包括3级腹泻（7个周期）、3级结肠炎（1个周期）、1例接受同期全肺放疗患者的3级肺炎、3-4级中性粒细胞减少（19个周期）和3-4级血小板减少（16个周期）。
伊立替康和替莫唑胺是一种耐受性良好且对复发性/进展性ES有效的方案。有必要进行前瞻性试验来确定该方案在新诊断ES中的作用。
