Neoadjuvant chemotherapy for Ewing's sarcoma of bone: no benefit observed after adding ifosfamide and etoposide to vincristine, actinomycin, cyclophosphamide, and doxorubicin in the maintenance phase--results of two sequential studies

Cancer. 1998 Mar 15;82(6):1174-83. doi: 10.1002/(sici)1097-0142(19980315)82:6<1174::aid-cncr24>;2-2.


Background: Ifosfamide (IF) alone or combined with etoposide (ET) was reported to be effective in the treatment of patients with Ewing's sarcoma who relapsed after treatment with the VACA regimen, which consisted of vincristine (VC), actinomycin (AC), cyclophosphamide (CP), and doxorubicin (AD). The purpose of this article is to report the results achieved in a new neoadjuvant protocol in which IF and ET were added to the conventional VACA regimen and administered to patients with localized disease.

Methods: In this study, eighty-two patients were treated between May 1988 and October 1991. Chemotherapy consisted of two induction cycles of VC/CP/AD followed by alternating cycles of VC/AD/CP, VC/IF/AC, IF/ET, and VC/CP/AC after local treatment. Twenty-two patients (27%) were treated with surgery only, 22 (27%) underwent surgery followed by radiation therapy, and 38 (46%) received radiotherapy only.

Results: At a median follow-up of 6.7 years (range, 4-9 years), 43 patients (52%) remained continuously disease free, and 39 relapsed (34 with metastases, 4 with local recurrence and metastases, and 1 with a local recurrence). These results were similar to those obtained at the same institute in a previous neoadjuvant study (March 1983 and April 1988) that included 108 patients treated with the conventional 4-drug regimen. The 5-year disease free and overall survival in the current study were 54% and 59%, respectively, and in the first study were 50% and 56%, respectively.

Conclusions: The comparison of these two sequential studies, although not randomized, referred to homogeneous groups of patients observed at the same institution who were treated by the same medical team. No advantage was observed when IF and ET were added to the VACA regimen.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / radiotherapy
  • Bone Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Child
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Dactinomycin / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Infusions, Intravenous
  • Injections, Intravenous
  • Male
  • Neoplasm Recurrence, Local
  • Sarcoma, Ewing / drug therapy*
  • Sarcoma, Ewing / radiotherapy
  • Sarcoma, Ewing / surgery
  • Vincristine / administration & dosage


  • Dactinomycin
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Ifosfamide

Supplementary concepts

  • VACA protocol