Patients with Ewing's sarcoma and a history of prior chemotherapy who show a poor histological response to VIDE induction, or who present with a tumour volume greater than 200 ml, require a defined next-line management strategy. This protocol addresses that specific clinical situation.
This protocol applies to patients with poor histological response to VIDE induction chemotherapy and/or a tumour volume greater than 200 ml. Randomised data indicate a survival advantage for patients in this high-risk subgroup when managed with an intensified approach.
The first-line regimen — VIDE induction chemotherapy (vincristine, ifosfamide, doxorubicin, etoposide), followed by local therapy and high-dose consolidation with busulfan and melphalan (BuMel) with autologous stem cell rescue, and adjuvant radiotherapy for eligible patients — aimed to achieve complete histological tumour response (100% necrosis, fibrosis, and calcification) on surgical specimen assessment and reduction in soft tissue mass size on MRI. When these goals are not met, escalation to this protocol is indicated.
Management at this stage involves second-line chemotherapy. Certain combination regimens — including those pairing alkylating agents with topoisomerase inhibitors — are among the options studied in this setting. Regimen selection is not standardised; the complete evidence-ranked protocol with full regimen options is available below.
DOI: 10.1016/j.annonc.2021.08.1995
The results of randomised studies with busulfan and melphalan (BuMel) indicated that this approach results in a survival advantage for patients with poor response to VIDE induction ChT and/or tumour volume >200 ml [II, A].
ChT regimens for relapsed ES are not standardised and include alkylating agents (cyclophosphamide and ifosfamide) in combination with topoisomerase inhibitors (etoposide and topotecan), irinotecan with temozolomide, gemcitabine and docetaxel, high-dose ifosfamide or carboplatin with etoposide [III, B].
Preliminary results from the rEECur study, the first randomised, controlled trial in this setting, suggest gemcitabine and docetaxel to be the inferior regimen, with temozolomide plus irinotecan also inferior to topotecan plus cyclophosphamide and high-dose ifosfamide.