Background: Large cooperative group studies have shown the efficacy of risk-adapted treatment for Ewing sarcoma (ES). However, validation and local adaptation by national cooperative groups is needed. A multicenter protocol to determine the efficacy and safety of adapted regimen was developed by the Latin American cooperative group (GALOP). The primary endpoint is investigate the feasibility and progression free survival (PFS) of combined modality therapy that incorporates interval-compressed VDC/IE as shown by the AEWS0031 study, and metronomic chemotherapy (CT). Secondary endpoints include safety, overall survival and duration of response. Methods: Induction (Indct) CT consisted of alternating cycles of VDC (vincristine 1.5 mg/m2 d1, doxorubicin 37.5 mg/m2 d1 and d2, cyclophosphamide 1.2 g/m2 d1) and IE (ifosfamide 3 g/m2 d1, d2 and d3, and etoposide 165 mg/m2 d1, d2 and d3), followed by local control. Pts with localized disease received 6 cycles at Indct and 8 at consolidation (Cons), and pts with metastasis received 9 at Indct and 5 at Cons. The time interval between cycles at Indct and Cons are 14 and 21 days, respectively. After Cons, pts with metastasis received metronomic CT, which consisted in oral cyclophosphamide (25 mg/m2/day, continuously) and vimblastin (3 mg/m2, weekly), for 1 year, while pts with localized disease are randomized (1:1) to receive or not metronomic CT according to the following risk factor: , age above versus (vs) below 14-years-old, pelvic vs non-pelvic primary tumor, tumor size more vs less than 8 cm, and male vs female. Toxicity is assessed following cycles of CT according to the CTC criteria. Enrollment began in April 2010, and, as of January 2011, 234 pts (107 with metastasis) have been recruited across 37 centers from Argentina, Brazil, Chile, and Uruguay. Statistical design: Target enrollment is 500 subjects; 200 pts with metastasis, and 300 pts with localized disease, of which 150 is randomized to the metronomic CT arm and 150 receive no further CT, in order to identify a difference in 5-years PFS of 15% (power 0.80, 2-tail type 1 error of 0.05).