High-Dose Chemotherapy and Autologous SCT vs Standard Chemotherapy in Localized High-Risk Ewing Sarcoma


Key Points

  • Patients who received high-dose therapy with busulfan and melphalan had improved progression-free and overall survival.
  • High-dose therapy with busulfan and melphalan was associated with a greater frequency of severe toxicities.

As reported in the Journal of Clinical Oncology by Whelan et al, combined trials (EURO-EWING99 and Ewing-2008) have shown evidence of improved outcomes with high-dose therapy with busulfan and melphalan (BuMel) and autologous stem cell transplant (SCT) vs standard chemotherapy with vincristine, dactinomycin, and ifosfamide (VAI) as consolidation in patients with localized high-risk Ewing sarcoma. The trial was stopped due to slow enrollment, reflecting in part low acceptability of the trial among parents/patients and physicians.  

Study Details

Overall, 240 patients were randomized between 2000 and 2015 to receive consolidation with BuMel plus autologous SCT (n = 122) or VAI (n = 118) after induction with 6 courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and 1 course of VAI. Patients had to be aged < 50 years with poor histologic response (≥ 10% viable cells) after VIDE or have tumor volume at diagnosis ≥ 200 mL if unresected, initially resected, or resected after radiotherapy. Patients had a median age of 17.1 years, and 78% had poor histologic response after chemotherapy alone.

Treatment Outcomes

Median follow-up was 7.8 years. In an intent-to-treat analysis, the risk of a disease event was significantly decreased in the BuMel group vs the VAI group (hazard ratio [HR] = 0.64, P = .026); event-free survival was 69.0% vs 56.7% at 3 years and 60.7% vs 47.1% at 8 years. The BuMel group had improved overall survival (HR = 0.63, P = .028); overall survival was 78.0% vs 72.2% at 3 years and 64.5% vs 55.6% at 8 years.


The BuMel group experienced significantly more severe acute toxicity than the VAI group, including significantly more gastrointestinal tract, liver, general condition, and hematologic severe adverse events and severe infections. Death occurred in two patients due to BuMel-related toxicity.

The investigators concluded, “BuMel improved [event-free survival] and [overall survival] when given after vincristine, ifosfamide, doxorubicin, and etoposide induction in localized [Ewing sarcoma] with predefined high-risk factors. For this group of patients, BuMel may be an important addition to the standard of care.”

The study was funded by multiple national and international government agencies and cancer charities.

Jeremy Whelan, MD, of the University College Hospital London, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.