Xu Jie, Xie Lu, Sun Xin, Liu Kuisheng, Liang Xin, Cai Zhenyu, Tang Xiaodong, Guo Wei
Peking University People's Hospital, Musculoskeletal Tumor Center, Beijing, P.R. China.
Peking University Shougang Hospital, Musculoskeletal Tumor Center, Beijing, P.R. China.
Clin Cancer Res. 2023 Mar 14;29(6):1040-1046. doi: 10.1158/1078-0432.CCR-22-3546.
The optimal dose schedule of vincristine, irinotecan, and temozolomide (VIT) in relapsed or refractory patients with Ewing sarcoma requires clarification.
Patients with relapsed or refractory Ewing sarcoma were randomly assigned (1:1) to either a shorter d × 5 schedule (irinotecan 50 mg/m2/d D1-5, vincristine 1.4 mg/m2 D1) or protracted d × 5×2 schedule (irinotecan 20 mg/m2/d D1-5,8-12, vincristine 1.4 mg/m2 D1,8) together with temozolomide (100 mg/m2/d D1-5). Patients were treated every 3 weeks for up to eight cycles until progression or unacceptable toxic effects occurred. The primary endpoint was objective response rate at 12 weeks (ORR12w). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.
A total of 46 patients presenting with relapsed or refractory Ewing sarcoma were randomly assigned to the d × 5 (n = 24) or d × 5×2 (n = 22) schedules. Median follow-up was 10.7 months in the d × 5 group and 8.3 months in the d × 5×2 group. ORR12w was lower for d × 5 (5/24; 20.8%) patients than for d × 5×2 (12/22; 54.5%; P = 0.019), but no significant difference was found in PFS (median PFS, 2.3 months for d × 5 vs. 4.3 months for d × 5×2) or OS (median OS, 14.8 months for d × 5 and 12.8 months for d × 5×2). Patients receiving the d × 5 schedule reported more grade 3 and 4 adverse events (AE) than those receiving d × 5×2, including diarrhea/abdominal pain and vomiting/nausea.
The protracted d × 5×2 VIT schedule showed superior efficacy and favorable tolerability compared with the shorter d × 5 VIT schedule in patients with relapsed or refractory Ewing sarcoma.
明确复发或难治性尤因肉瘤患者中长春新碱、伊立替康和替莫唑胺（VIT）的最佳给药方案。
复发或难治性尤因肉瘤患者被随机分配（1:1）至较短的d×5方案（伊立替康50mg/m²/d，第1 - 5天；长春新碱1.4mg/m²，第1天）或延长的d×5×2方案（伊立替康20mg/m²/d，第1 - 5天、第8 - 12天；长春新碱1.4mg/m²，第1天、第8天），同时联合替莫唑胺（100mg/m²/d，第1 - 5天）。患者每3周治疗一次，最多进行8个周期，直至疾病进展或出现不可接受的毒性反应。主要终点为12周时的客观缓解率（ORR12w）。次要终点为无进展生存期（PFS）、总生存期（OS）和安全性。
共有46例复发或难治性尤因肉瘤患者被随机分配至d×5方案组（n = 24）或d×5×2方案组（n = 22）。d×5组的中位随访时间为10.7个月，d×5×2组为8.3个月。d×5方案组患者的ORR12w（5/24；20.8%）低于d×5×2方案组（12/22；54.5%；P = 0.019），但在PFS（d×5方案组中位PFS为2.3个月，d×5×2方案组为4.3个月）或OS（d×5方案组中位OS为14.8个月，d×5×2方案组为12.8个月）方面未发现显著差异。接受d×5方案的患者报告的3级和4级不良事件（AE）比接受d×5×2方案的患者更多，包括腹泻/腹痛和呕吐/恶心。
在复发或难治性尤因肉瘤患者中，与较短的d×5 VIT方案相比，延长的d×5×2 VIT方案显示出更好的疗效和耐受性。
