Ifosfamide and etoposide plus vincristine, doxorubicin, and cyclophosphamide for newly diagnosed Ewing's sarcoma family of tumors

Cancer. 1996 Aug 15;78(4):901-11. doi: 10.1002/(SICI)1097-0142(19960815)78:4<901::AID-CNCR30>3.0.CO;2-X.


Background: This study was conducted to determine the feasibility of, and improve outcome by, incorporating ifosfamide and etoposide (IE) into the therapy of newly diagnosed patients with Ewing's sarcoma family of tumors of bone and soft tissue.

Methods: Fifty-four newly diagnosed patients received 7 cycles of vincristine, doxorubicin, and cyclophosphamide (VAdriaC) and 11 cycles of IE. Radiation therapy after the fifth chemotherapy cycle was the primary approach to local control.

Results: Actuarial 5-year event-free survival (EFS) and overall survival rates were 42% and 45%, respectively, with a median duration of potential follow-up of 6.8 years. EFS was significantly better for patients with localized tumors than for those with metastatic lesions (64% v. 13%, P < 0.0001). Actuarial local progression-free survival at 5 years was 74%, and did not correlate with primary tumor size or site, histologic subtype, or the presence of metastases. Febrile neutropenia developed after 49% of cycles, and clinical or sub-clinical cardiac dysfunction was common (7% and 40% respectively). There were four toxic deaths and one case of secondary myelodysplastic syndrome.

Conclusions: Despite substantial toxicity, the integration of IE into the front-line, VAdriaC-based therapy of patients with Ewing's sarcoma family of tumors is feasible and appeared to significantly improve the outcome for patients with high risk localized tumors, but had no impact on the poor prognosis of patients with metastatic tumors. Local control can be achieved in the vast majority of patients using radiotherapy exclusively, even among patients with bulky, central axis tumors. Longer follow-up is needed to evaluate the late effects of this intensive therapy.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Child
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Heart Failure / chemically induced
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / adverse effects
  • Male
  • Neutropenia / chemically induced
  • Pilot Projects
  • Sarcoma, Ewing / drug therapy*
  • Soft Tissue Neoplasms / drug therapy*
  • Thrombocytopenia / chemically induced
  • Vincristine / administration & dosage


  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Ifosfamide

Supplementary concepts

  • CAV protocol
  • IE protocol