Ifosfamide, carboplatin, and etoposide for neuroblastoma: a high-dose salvage regimen and review of the literature

Cancer. 2013 Feb 1;119(3):665-71. doi: 10.1002/cncr.27783. Epub 2012 Sep 5.


Background: The authors report a retrospective analysis of high-dose ifosfamide, carboplatin, and etoposide (HD-ICE) for patients with refractory or relapsed neuroblastoma (NB). A major reason for using this regimen was the long time since patients received previous treatment with a platinum compound. The authors also summarized the published experience on ICE in patients with NB.

Methods: Treatment comprised ifosfamide (2000 mg/m(2) daily for 5 days), carboplatin (500 mg/m(2) daily for 2 days), and etoposide (100 mg/m(2) daily for 5 days). Patients who had poor hematologic reserve (platelet count <100,000/μL) from previous therapy received peripheral blood stem cells (PBSCs) after HD-ICE. Disease status before and after HD-ICE was defined according to International Neuroblastoma Response Criteria (expanded to include (123) I-metaiodobenzylguanidine findings). Publications that were informative about ICE for NB were reviewed.

Results: Seventy-four patients received 92 cycles of ICE, including 37 patients who received PBSC rescue. Grade 3 toxicities were rare: 1-3 patients had encephalopathy, mucositis, or gastroenteritis. Bacteremia was documented in 24 of 92 cycles (26%). The absolute neutrophil count reached 500/μL on day 17-30 (median, day 22) in patients who had satisfactory hematologic reserve. Disease regressions (major and minor responses) were achieved by 14 of 17 patients (82%) with a new relapse, 13 of 26 patients (50%) with refractory NB, and 12 of 34 patients (35%) who were treated for progressive disease during chemotherapy (P = .005). In the literature, patients received ICE at lower dosages and achieved major response rates >36% in phase 1 and 2 studies (in which less comprehensive staging evaluations were used) that involved resistant NB and >70% in induction for newly diagnosed NB.

Conclusions: HD-ICE is appealing as salvage treatment or consolidative therapy because of its anti-NB activity and the low risk of major nonhematologic toxicity. PBSC support is unnecessary for patients who had intact hematologic reserve.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bone Marrow Neoplasms / drug therapy
  • Bone Marrow Neoplasms / epidemiology
  • Carboplatin / administration & dosage*
  • Carboplatin / adverse effects
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Etoposide / administration & dosage*
  • Etoposide / adverse effects
  • Female
  • Humans
  • Ifosfamide / administration & dosage*
  • Ifosfamide / adverse effects
  • Infant
  • Male
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / epidemiology
  • Retrospective Studies
  • Salvage Therapy / methods
  • Soft Tissue Neoplasms / drug therapy
  • Soft Tissue Neoplasms / epidemiology
  • Young Adult


  • Etoposide
  • Carboplatin
  • Ifosfamide