title: Ifosfamide, carboplatin, and etoposide for neuroblastoma: a high-dose salvage regimen and review of the literature.
abstract: 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.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. kushnerb@mskcc.org
authors.forename: Brian H
authors.initials: BH
authors.lastname: Kushner
authors.forename: Shakeel
authors.initials: S
authors.lastname: Modak
authors.forename: Kim
authors.initials: K
authors.lastname: Kramer
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Basu
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Roberts
authors.forename: Nai-Kong V
authors.initials: NK
authors.lastname: Cheung
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D019046:Bone Marrow Neoplasms / Q000188:drug therapy / Q000453:epidemiology; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy* / Q000453:epidemiology; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000453:epidemiology; D055815:Young Adult
chemical_list: D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide