Longer versus Shorter Schedules of Vincristine, Irinotecan, and Temozolomide (VIT) for Relapsed or Refractory Ewing Sarcoma: A Randomized Controlled Phase 2 Trial

Purpose: The optimal dose schedule of vincristine, irinotecan, and temozolomide (VIT) in relapsed or refractory patients with Patients and Methods: Patients with relapsed or refractory Ewing sarcoma were randomly assigned (1:1) to either a shorter 1.4 mg/m2 D1) or protracted d x 5x2 schedule (irinotecan 20 mg/m2/d D1-5,8-12, vincristine 1.4 mg/m2 D1,8) together with 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), andResult: A total of 46 patients presenting with relapsed or refractory Ewing sarcoma were randomly assigned to the d x 5 (n = 24) or d x 5x2 (n = 22) schedules. Median follow-up was 10.7 months in the d x 5 group and 8.3 months in the d x 5x2 group. ORR12w was lower ford x 5 (5/24; 20.8%) patients than for d x 5x2 (12/ 22; 54.5%; P = 0.019), but no significant difference was found in PFS (median PFS, 2.3 months for d x 5 vs. 4.3 months for d x 5x2) or OS (median OS, 14.8 months for d x 5 and 12.8 months ford x 5x2). Patients receiving the d x 5 schedule reported more grade 3 and 4 adverse events (AE) than those receiving d x 5x2, including diarrhea/abdominal pain and vomiting/nausea. Conclusions: The protracted d x 5x2 VIT schedule showed super-ior efficacy and favorable tolerability compared with the shorter d x 5 VIT schedule in patients with relapsed or refractory Ewing sarcoma.