ICE Regimen for Relapsed/Refractory Bone and Soft Tissue Sarcomas in Children

Rev Recent Clin Trials. 2018;13(2):126-131. doi: 10.2174/1574887113666180124114818.


Background: The outcome of bone and soft tissue sarcomas (BST) after relapse has very poor prognosis with survival rates less than 39%. Unfortunately there are not many treatment options, but promising responses have been reported with ifosfamide, etoposide and carboplatin (ICE).

Objective: Therefore, we planned a study for children with recurrent/refractory BST treated with ICE regimen to evaluate their demographic features, responses to treatment and outcome.

Method: Patients with primary diagnosis of BST and treated with ICE regimen at the time of first or subsequent relapse, progression or unresponsive disease were selected for study. The files were retrospectively evaluated.

Results: Thirty of sixty-six patients had metastatic disease at relapse. Patients received median 5 cycles of ICE and were followed-up median 16.3 months. Overall survival rates were 83% and 62% at 1st and 2nd year. The ORR to the regimen was 43%. Survival rates were significantly higher in good responders (3-year EFS and OS rates: 50% vs. 8% and 78% vs. 14%; p<0.0001 and p<0.0001). Survival rates for non-metastatic disease were 42% and 75% for EFS and OS and higher than patients with metastases at relapse (p<0.001 and p<0.0001). EFS and OS rates of patients with rhabdomyosarcoma were 42% and 69%. No grade 3 or 4 renal toxicity was documented.

Conclusion: ICE combination improves the outcome of relapsed or refractory sarcomas and it might serve as second line treatment. Patients with no metastases at relapse would benefit more than others with metastatic disease.

Keywords: Chemotherapy; ICE regimen; ifosfamide; relapsed sarcoma; soft tissue sarcomas (BST); treatment..

MeSH terms

  • Adolescent
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology
  • Carboplatin / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Therapy, Combination
  • Etoposide / therapeutic use*
  • Female
  • Humans
  • Ifosfamide / therapeutic use*
  • Infant
  • Male
  • Retrospective Studies
  • Sarcoma / drug therapy*
  • Sarcoma / mortality
  • Sarcoma / pathology
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / mortality
  • Soft Tissue Neoplasms / pathology


  • Antineoplastic Agents
  • Etoposide
  • Carboplatin
  • Ifosfamide