The optimal dose schedule of vincristine, irinotecan and temozolomide (VIT) in relapsed or refractory Ewing sarcoma patients requires clarification.

Patients with relapsed or refractory Ewing sarcoma were randomly assigned (1:1) to either a shorter dx5 schedule (irinotecan 50mg/m2/d D1-5, vincristine 1.4mg/m2 D1) or protracted dx5x2 schedule (irinotecan 20mg/m2/d D1-5,8-12, vincristine 1.4mg/m2 D1,8) together with temozolomide (100mg/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 dx5 (n=24) or dx5x2(n=22) schedules. Median follow-up was 10.7 months in the dx5 group and 8.3 months in the dx5x2 group. ORR12w was lower for dx5 (5/24 [20.8%]) patients than for dx5x2 (12/22[54.5%]; p=0.019), but no significant difference was found in PFS ( median PFS: 2.3 months for dx5 vs 4.3 months for dx5x2) or OS (median OS: 14.8 months for dx5 and 12.8 months for dx5x2). Patients receiving the dx5 schedule reported more grade 3 and 4 adverse events (AEs) than those receiving dx5x2, including diarrhea/abdominal pain, vomiting/nausea.

The protracted dx5x2 VIT schedule showed superior efficacy and favorable tolerability compared with the shorter dx5 VIT schedule in patients with relapsed or refractory Ewing sarcoma.