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


Authors: Kushner, B. H.; Modak, S.; Kramer, K.; Basu, E. M.; Roberts, S. S.; Cheung, N. K. V.
Article 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/m2 daily for 5 days), carboplatin (500 mg/m2 daily for 2 days), and etoposide (100 mg/m2 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 123I-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. Cancer 2013. © 2012 American Cancer Society.
Keywords: child; controlled study; preschool child; school child; treatment response; major clinical study; salvage therapy; cisplatin; side effect; cancer patient; drug megadose; carboplatin; multiple cycle treatment; neutrophil count; bone marrow suppression; etoposide; mucosa inflammation; cyclophosphamide; retrospective study; ifosfamide; infant; neuroblastoma; brain disease; remission; single drug dose; drug dose regimen; peripheral blood stem cell transplantation; bacterial infection; hemorrhagic cystitis; respiratory tract disease; hematology; gastroenteritis; novel therapeutics; peripheral blood stem cells
Journal Title: Cancer
Volume: 119
Issue: 3
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2013-02-01
Start Page: 665
End Page: 671
Language: English
DOI: 10.1002/cncr.27783
PROVIDER: scopus
PUBMED: 22951749
DOI/URL:
Notes: --- - "Export Date: 1 March 2013" - "CODEN: CANCA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Brian Kushner
    191 Kushner
  2. Nai-Kong Cheung
    446 Cheung
  3. Kim Kramer
    170 Kramer
  4. Shakeel Modak
    160 Modak
  5. Ellen Marlese Basu
    34 Basu
  6. Stephen Stacy Roberts
    41 Roberts