Carboplatin in the treatment of Ewing sarcoma: Results of the first Brazilian collaborative study group for Ewing sarcoma family tumors-EWING1

Pediatr Blood Cancer. 2015 Oct;62(10):1747-53. doi: 10.1002/pbc.25562. Epub 2015 Apr 27.

Abstract

Background: Large cooperative group studies have shown the efficacy of risk-adapted treatment for Ewing sarcoma. However, validation and local adaptation by National cooperative groups is needed. A multicenter protocol to determine the efficacy and safety of a risk-adapted intensive regimen was developed by the Brazilian cooperative group.

Procedure: Patients <30 years old with Ewing sarcoma were eligible. Induction chemotherapy consisted of two cycles of ICE (ifosfamide, carboplatin, and etoposide) followed by two cycles of VDC (vincristine, doxorubicin, and cyclophosphamide), followed by local control. Patients with low risk (LR) disease (localized resectable with normal LDH) received 10 additional alternating courses of IE with VDC. For patients with high-risk (HR) disease (unresectable, pelvic, metastatic, or high LDH), two additional cycles of ICE were given.

Results: One-hundred seventy five patients (39% metastatic) were enrolled. Fifty-two patients (29.7%) were LR and 123 (70.3%) were HR. Overall response rate at end of induction was 27.4%. Five-year event-free survival (EFS) and overall survival (OS) estimates were 51.4% and 54.4%, respectively. Patients with localized disease had better outcomes than patients with metastases (5-year EFS 67.9% vs. 25.5%, and 5-year OS 70.3% vs. 29.1%, respectively). On multivariate analysis, the presence of metastatic disease was the only prognostic factor (P < 0.01).

Conclusion: The VDC/ICE protocol was feasible, and considering the high tumor burden in our population, resulted in comparable results to those reported by cooperative groups in high-income countries. Further adaptation to maximize efficacy and minimize toxicity will be required.

Keywords: Ewing/PNET; VDC/ICE; metastatic disease.

Publication types

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

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / mortality
  • Brazil
  • Carboplatin / administration & dosage*
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Etoposide
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Induction Chemotherapy / methods
  • Infant
  • Infant, Newborn
  • Kaplan-Meier Estimate
  • Male
  • Proportional Hazards Models
  • Sarcoma, Ewing / drug therapy*
  • Sarcoma, Ewing / mortality
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / mortality
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Carboplatin
  • Ifosfamide