Study Aim: Patients with high-risk Ewing sarcoma (ES) have dismal outcomes despite aggressive multimodal therapy. This phase II, single-institution study evaluated the response rate to two up-front cycles of irinotecan, temozolomide, and temsirolimus (ITT) and assessed the tolerability of maintenance therapy following standard treatment in high-risk ES. Methods: Eligible patients had newly diagnosed high-risk ES (age ≥14 years old, metastatic disease, or primary pelvic tumor). The therapy included two cycles of window therapy (ITT) followed by interval-compressed chemotherapy (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide) and maintenance therapy (cyclophosphamide, sorafenib, and bevacizumab). A two-stage sequential design was employed to assess a >50% WHO response (CR or PR) with 80% power. Patients who required emergent radiation were excluded from receiving window therapy. Results: Sixteen patients (median age 12.2 years; range 4.8–23.6 years) were enrolled (12 evaluable for overall response, 10 for primary tumor response). Only three achieved a PR to window therapy, leading to study closure. All evaluable patients demonstrated a decline in their primary tumor volume (mean decline: 32.5%, standard deviation: 17.6%,p-value: 0.0005) and SUV peak (mean decline: 49.9%, standard deviation: 21.1%,p-value: 0.002). Maintenance therapy was well tolerated, with only 2/13 patients discontinuing due to toxicity. Conclusions: ITT did not achieve the prespecified response rate of 50%, according to WHO criteria; however, all patients exhibited decreased volume and metabolic activity, highlighting the limitations of conventional response assessments. Maintenance therapy was feasible and well tolerated. Although limited by small sample size, heterogeneous disease presentations, and the absence of a control arm, this study supports further evaluation of ITT and a maintenance approach in larger, randomized trials for high-risk ES.
研究目的：高危尤文肉瘤（ES）患者即使接受积极的综合治疗，预后仍极差。这项单中心II期研究评估了高危ES患者对两个前期伊立替康、替莫唑胺和替西罗莫司（ITT）治疗周期的反应率，并评估了标准治疗后维持治疗的耐受性。方法：符合条件的患者为新诊断的高危ES（年龄≥14岁、转移性疾病或盆腔原发肿瘤）。治疗方案包括两个周期的窗口期治疗（ITT），随后进行间隔压缩化疗（长春新碱、多柔比星和环磷酰胺与异环磷酰胺和依托泊苷交替使用）以及维持治疗（环磷酰胺、索拉非尼和贝伐珠单抗）。采用两阶段序贯设计评估>50%的WHO反应率（完全缓解或部分缓解），检验效能为80%。需要紧急放疗的患者被排除在窗口期治疗之外。结果：共纳入16例患者（中位年龄12.2岁；范围4.8-23.6岁）（12例可评估总体反应，10例可评估原发肿瘤反应）。仅3例患者对窗口期治疗达到部分缓解，导致研究提前终止。所有可评估患者的原发肿瘤体积均有所下降（平均下降：32.5%，标准差：17.6%，p值：0.0005），SUV峰值亦下降（平均下降：49.9%，标准差：21.1%，p值：0.002）。维持治疗耐受性良好，13例患者中仅2例因毒性反应停药。结论：根据WHO标准，ITT未达到预设的50%反应率；然而，所有患者的肿瘤体积和代谢活性均有所下降，凸显了传统反应评估的局限性。维持治疗可行且耐受性良好。尽管本研究受限于样本量小、疾病表现异质性以及缺乏对照组，但支持在更大规模的随机试验中进一步评估ITT及维持治疗方案在高危ES中的应用。
肿瘤(癌症)患者之家