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Ewing Sarcoma: Localized Tumors

    Standard Treatment Options

    Because most patients with apparently localized disease at diagnosis have occult metastatic disease, multidrug chemotherapy as well as local disease control with surgery and/or radiation is indicated in the treatment of all patients.[1,2,3,4,5,6,7,8] Current regimens for the treatment of localized Ewing sarcoma achieve event-free survival (EFS) and overall survival (OS) of approximately 70% at 5 years after diagnosis.[9]

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    Current standard chemotherapy in the United States includes vincristine, doxorubicin, and cyclophosphamide, also known as VAdriaC or VDC, alternating with ifosfamide and etoposide (IE).[9] The combination of IE has shown activity in Ewing sarcoma, and a large randomized clinical trial and a nonrandomized trial demonstrated that outcome was improved when IE was alternated with VAdriaC.[2,9,10] Dactinomycin is no longer used in the United States but continues to be used in the Euro-Ewing studies. Increased dose intensity of doxorubicin during the initial months of therapy was associated with an improved outcome in a meta-analysis done prior to the standard use of ifosfamide and etoposide.[11] The use of high-dose VAdriaC has shown promising results in small numbers of patients.[11] A single institution study of 44 patients treated with high-dose VAdriaC and IE had an 82% 4-year EFS.[12] However, in an intergroup trial of the Pediatric Oncology Group and the Children's Cancer Group, which compared a dose-intensified chemotherapy regimen of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC/IE) with standard doses of the same regimen, no differences in outcome were observed.[13] Unlike the single institution trial, this trial did not maintain the dose intensity of alkylating agents for the duration of treatment.[12]

    In a completed Children's Oncology Group (COG) trial (COG-AEWS0031), 568 patients with newly diagnosed localized extradural Ewing sarcoma were randomly assigned to receive chemotherapy (VAdriaC alternating with IE) given every 2 weeks (interval compression) versus every 3 weeks (standard). Patients randomly assigned to the every 2-week interval of treatment had an improved 5-year EFS (73% vs. 65%, P = .048). There was no increase in toxicity observed with the every 2-week schedule.[14]

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