High-Dose Busulfan Plus Melphalan Consolidation Therapy May Improve Outcomes in Ewing Sarcoma

Share this content:
Previous studies have suggested that high-dose therapy with busulfan plus melphalan may confer a benefit to patients with Ewing sarcoma compared with conventional chemotherapy.
Previous studies have suggested that high-dose therapy with busulfan plus melphalan may confer a benefit to patients with Ewing sarcoma compared with conventional chemotherapy.

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 (ClinicalTrials.gov Identifier: NCT00020566) and EWING-2008 (ClinicalTrials.gov 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.

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.

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.”

Reference

  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

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Sign Up for Free e-newsletters



Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs