This protocol addresses the clinical scenario in which Ewing's sarcoma has relapsed or progressed following completion of first-line induction chemotherapy and local therapy, and the expected response targets were not met.
The prior treatment was interval-compressed VDC/IE induction chemotherapy (vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide) or, alternatively, the VIDE induction regimen (vincristine, ifosfamide, doxorubicin, etoposide), followed by local therapy and adjuvant or consolidation chemotherapy.
Escalation to this second-line protocol is indicated when the following goals were not achieved: complete histological tumour response (100% necrosis, fibrosis, and calcification on surgical specimen assessment) and/or adequate reduction in size of the soft tissue mass on MRI.
Second-line treatment for relapsed Ewing's sarcoma involves combination chemotherapy regimens that incorporate alkylating agents. Several options are available, and the choice between them is now informed by evidence from the rEECur randomised controlled trial — the first prospective head-to-head comparison in this relapsed setting. The complete regimen options, selection criteria, and structured algorithm are in the full protocol below.