In light of the recent rEECur trial interim analysis, would you offer high-dose ifosfamide to an AYA patient with relapsed Ewing's sarcoma who initially had a complete response to up-front therapy?

Yes, I would certainly consider offering high-dose ifosfamide to relapsed Ewing's sarcoma patients in light of the rEECur results [McCabe et al., J Clin Oncol 40, 2022 (suppl 17; abstr LBA2)]. The first line regimens I have traditionally offered to recurrent EWS patients have been topotecan/cyclophosphamide or vincristine/irinotecan/temozolomide, and while numbers were not huge, the rEECur results would suggest that high dose ifosfamide may be more effective than either regimen. This is particularly pertinent as many patients included in this European study likely received higher doses ifosfamide during their initial therapy than most American patients will have had up front. It is worth bearing in mind, however, that patients receiving hig...

It is correct that the rEECur study concluded that high dose ifosfamide was superior in a non-significant comparison against cyclophosphamide/topotecan or irinotecan/temozolomide. However, in that study, the irinotecan/topotecan regimen used a 5-day schedule of irinotecan. A retrospective review of published series compared the results of treatment with irinotecan and temozolomide with a 10-day schedule to treatment with a 5-day schedule. [Slotkin and Meyers, PMID 36184748.] Among 89 patients treated with a 10-day irinotecan schedule, there were 47 objective responses (53%). Among 180 patients treated with a 5-day irinotecan schedule, there were 52 responses (29%). Two studies which used the 5-day irinotecan schedule reported median times t...