Results of the EICESS-92 Study: two randomized trials of Ewing's sarcoma treatment--cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients-

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647 patients with localized Ewing sarcoma were sorted into two risk groups based on the stage and tumour volume. Patients were allocated to the standard-risk (SR) group if their localized tumours were less than 100 mL in volume. Patients with localized tumours greater than 100 mL or with metastatic disease were allocated to the high-risk (HR) group. The 155 SR patients were then randomized to receive 4 courses of vincristine, dactinomycin, ifosfamide, and doxorubicin (VAIA) induction therapy, followed by 10 courses of either VAIA or vincristine, dactinomycin, cyclophosphamide, and doxorubicin (VACA) therapy, in order to compare the efficacy of ifosfamide versus cyclophosphamide. The 492 HR patients were randomized to receive 14 courses VAIA therapy alone or VAIA therapy and etoposide (EVAIA), in order to evaluate the impact of etoposide on survival. Following 8.5 years, results indicated that VACA and VAIA therapies provided similar survival rates in SR patients, while the addition of etoposide to VAIA therapy appeared to increase the survival rate in HR patients. It should be noted though that SR patients in the VACA group experienced a higher occurrence of acute grade 3 or 4 toxicities, mucositis, and infection and HR patients in the EVAIA group had a higher occurrence of hematologic toxicities.