Nonmetastatic Ewing family tumors: high-dose chemotherapy with stem cell rescue in poor responder patients. Results of the Italian Sarcoma Group/Scandinavian Sarcoma Group III protocol

Ann Oncol. 2011 May;22(5):1221-1227. doi: 10.1093/annonc/mdq573. Epub 2010 Nov 8.

Abstract

Background: High-dose chemotherapy (HDT) was added to conventional chemotherapy in Ewing sarcoma family tumor (EFT) patients, poor responders (PRs) to induction chemotherapy in order to improve their survival.

Patients and methods: Patients aged ≤40 years with nonmetastatic Ewing sarcoma (ES) received vincristine (V), doxorubicin (A), cyclofosfamide (C), actinomycin (Ac), ifosfamide (I) and etoposide (E) (VACAc-IE regimen) as induction chemotherapy. As maintenance treatment, good responders (GR) received nine cycles of VACAc-IE regimen. PRs received three cycles of VAC-IE, mobilizing cycle with CE and HDT with Busulfan and Melphalan with stem cell support.

Results: Three hundred patients [median age 15 years (3-40 years)] entered the study. One patient refused local treatment, 242 (81%) underwent surgery [with radiotherapy (RT) in 80] and 57 (19%) RT alone. No toxic deaths were recorded. Overall GR were 146 (49%). Twenty-eight PR did not receive HDT. At a median follow-up of 64 months (21-116 months), 5-year overall and event-free survival (EFS) were 75% and 69%, respectively. Five-year EFS was 75% for GR, 72% for PR treated with HDT and 33% for PR who did not receive HDT.

Conclusions: High-dose therapy added to the VACA-IE regimen in PR patients is feasible and effective. Selected groups of patients with ES can benefit from HDT.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / therapy*
  • Busulfan / therapeutic use
  • Child
  • Child, Preschool
  • Cyclophosphamide / therapeutic use
  • Dactinomycin / therapeutic use
  • Disease-Free Survival
  • Doxorubicin / therapeutic use
  • Etoposide / therapeutic use
  • Female
  • Humans
  • Ifosfamide / therapeutic use
  • Kaplan-Meier Estimate
  • Male
  • Melphalan / therapeutic use
  • Myeloablative Agonists / therapeutic use
  • Peripheral Blood Stem Cell Transplantation*
  • Sarcoma, Ewing / mortality
  • Sarcoma, Ewing / therapy*
  • Vincristine / therapeutic use
  • Young Adult

Substances

  • Myeloablative Agonists
  • Dactinomycin
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Busulfan
  • Melphalan
  • Ifosfamide

Supplementary concepts

  • IE protocol
  • VACA protocol