Vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) induction therapy followed by busulfan plus melphalan (BuMel) may improve overall survival (OS) and event-free survival (EFS) among patients with localized Ewing sarcoma (ES) and predefined high-risk factors, according to a study published in the Journal of Clinical Oncology.1

Previous studies have suggested that high-dose therapy with BuMel may confer a benefit to patients with ES when compared with conventional chemotherapy, but there is a paucity of head-to-head comparative data.

For the Euro-E.W.I.N.G.99 ( Identifier: NCT00020566) and EWING-2008 ( Identifier: NCT00987636) phase 3 studies, researchers enrolled 240 patients with EW classified as high risk who underwent VIDE induction therapy. Patients were randomly assigned to receive consolidation therapy with 7 courses of standard chemotherapy (vincristine, dactinomycin, ifosfamide [VAI]) or 1 high-dose course of BuMel. Follow-up was performed every 3 months for the first 3 years, then every 6 months for years 4 and 5, then annually.

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After a median follow-up of 7.8 years, results showed that patients who received BuMel had a significantly reduced risk of event compared with those receiving VAI (hazard ratio [HR], 0.64; 95% CI, 0.43-0.95; P = .026). Three-year EFS rates for BuMel compared with VAI were 69.0% (95% CI, 60.2-76.6) versus 56.7% (95% CI, 47.6-65.4), respectively, and 8-year EFS rates were 60.7% (95% CI, 51.1-69.6) versus 47.1% (95% CI, 37.7-56.8), respectively.

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Patients treated with BuMel also had improved OS (HR, 0.63; 95% CI, 0.41-0.95; P = .028). The 3-year OS rate for the BuMel group was 78.0% (95% CI, 69.6-84.5) compared with 72.2% (95% CI, 63.3-79.6) for the VAI group. The 8-year OS rate was 64.5% (95% CI, 54.4-73.5) in the BuMel group compared with 55.6% (95% CI, 45.8-65.1) in the VAI group.

Patients treated with BuMel had improved EFS and OS outcomes but experienced a significantly higher rate of adverse events, and 2 BuMel treatment-related mortalities were reported. The investigators added, however, that these adverse events were transient and occurred only once after BuMel compared with numerous toxicities after multiple VAI courses.

The authors concluded that “the reliable demonstration of EFS and OS improvement indicates that BuMel may be considered as a standard of care for patients with localized ES fulfilling the definition of high-risk disease used in this trial and no contraindication to BuMel.”


  1. Whelan J, Le Deley MC, Dirksen U, et al. High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk Ewing sarcoma: results of Euro-E.W.I.N.G.99 and Ewing-2008 [published online September 6, 2018]. J Clin Oncol. doi: 10.1200/JCO.2018.78.2516