a Istituto Ortopedico Rizzoli , Bologna , Italy.
b Royal Marsden Hospital and Institute of Cancer Research , London , UK.
Acta Oncol. 2018 Jul;57(7):958-964. doi: 10.1080/0284186X.2018.1449250. Epub 2018 Mar 13.
Data on temozolomide (TEM) and irinotecan (IRI) activity in recurrent Ewing sarcoma (EWS), especially in adult patients, are limited.
Patients receiving TEM 100 mg/m/day oral, and IRI 40 mg/m/day intravenous, days 1-5, every 21 days, were included in this multi-institutional retrospective study. Disease control rate (DCR) [overall response rate (ORR) [complete response (CR) + partial response (PR)] + stable disease (SD)], 6-months progression-free survival (6-mos PFS) and 1-year overall survival (OS) were assessed.
The median age of the 51 patients was 21 years (range 3-65 years): 34 patients (66%) were adults (≥18 years of age), 24 (48%) had ECOG 1 and 35 (69%) were presented with multiple site recurrence. TEMIRI was used at first relapse/progression in 13 (25%) patients, while the remainder received TEMIRI for second or greater relapse/progression. Fourteen (27%) patients had received prior myeloablative therapy with busulfan and melphalan. We observed five (10%) CR, 12 (24%) PR and 19 (37%) SD, with a DCR of 71%. 6-mos PFS was 49% (95% CI 35-63) and it was significantly influenced by ECOG (6-mos PFS 64% [95% CI 45-83] for ECOG 0, 34% [95% CI 14-54] for ECOG ≥1; p = .006) and LDH (6-mos PFS 62% [95% CI 44-79] for normal LDH, 22% [95% CI 3-42] for high LDH; p = .02), with no difference according to line of treatment, age and metastatic pattern. One-year OS was 55% (95% CI 39-70), with RECIST response (p = .001) and ECOG (p = .0002) independently associated with outcome. Grade 3 and 4 toxicity included neutropenia in 12% of patients, thrombocytopenia in 4%, diarrhea in 4%.
This series confirms the activity of TEMIRI in both adults and pediatric patients. This schedule offers a 71% DCR, independently of the line of chemotherapy. Predictive factors of response are ECOG and LDH.
关于替莫唑胺（TEM）和伊立替康（IRI）在复发性尤因肉瘤（EWS）中的活性的数据，特别是在成人患者中的数据有限。
本多机构回顾性研究纳入了接受 TEM 100mg/m/天口服和 IRI 40mg/m/天静脉滴注，第 1-5 天，每 21 天一次的患者。评估疾病控制率（DCR）[总缓解率（ORR）[完全缓解（CR）+部分缓解（PR）]+稳定疾病（SD）]、6 个月无进展生存期（6-mos PFS）和 1 年总生存期（OS）。
51 例患者的中位年龄为 21 岁（范围 3-65 岁）：34 例（66%）为成人（≥18 岁），24 例（48%）ECOG 评分为 1 分，35 例（69%）为多发病灶复发。13 例（25%）患者在首次复发/进展时接受 TEMIRI 治疗，其余患者接受 TEMIRI 治疗用于第二次或以上复发/进展。14 例（27%）患者接受过含白消安和马法兰的大剂量化疗。我们观察到 5 例（10%）CR、12 例（24%）PR 和 19 例（37%）SD，DCR 为 71%。6-mos PFS 为 49%（95%CI 35-63），ECOG（6-mos PFS 64%[95%CI 45-83] vs ECOG≥1 的 34%[95%CI 14-54]；p=0.006）和 LDH（6-mos PFS 62%[95%CI 44-79] vs 正常 LDH 的 22%[95%CI 3-42]；p=0.02）显著影响 6-mos PFS，与治疗线数、年龄和转移模式无关。1 年 OS 为 55%（95%CI 39-70），RECIST 缓解（p=0.001）和 ECOG（p=0.0002）与预后独立相关。3-4 级毒性包括中性粒细胞减少 12%、血小板减少 4%、腹泻 4%。
本系列研究证实了 TEMIRI 在成人和儿科患者中的活性。该方案的疾病控制率为 71%，与化疗线数无关。反应的预测因素是 ECOG 和 LDH。
