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

Abstract

<div>AbstractPurpose:<p>The optimal dose schedule of vincristine, irinotecan, and temozolomide (VIT) in relapsed or refractory patients with Ewing sarcoma requires clarification.</p>Patients and Methods:<p>Patients with relapsed or refractory Ewing sarcoma were randomly assigned (1:1) to either a shorter d × 5 schedule (irinotecan 50 mg/m<sup>2</sup>/d D<sub>1–5</sub>, vincristine 1.4 mg/m<sup>2</sup> D<sub>1</sub>) or protracted d × 5×2 schedule (irinotecan 20 mg/m<sup>2</sup>/d D<sub>1–5,8–12</sub>, vincristine 1.4 mg/m<sup>2</sup> D<sub>1,8</sub>) together with temozolomide (100 mg/m<sup>2</sup>/d D<sub>1–5</sub>). 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 (ORR<sub>12w</sub>). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.</p>Result:<p>A total of 46 patients presenting with relapsed or refractory Ewing sarcoma were randomly assigned to the d × 5 (<i>n</i> = 24) or d × 5×2 (<i>n</i> = 22) schedules. Median follow-up was 10.7 months in the d × 5 group and 8.3 months in the d × 5×2 group. ORR<sub>12w</sub> was lower for d × 5 (5/24; 20.8%) patients than for d × 5×2 (12/22; 54.5%; <i>P</i> = 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.</p>Conclusions:<p>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.</p></div>