Ifosfamide/carboplatin/etoposide (ICE) as front-line, topotecan/cyclophosphamide as second-line and oral temozolomide as third-line treatment for advanced neuroblastoma over one year of age

Acta Paediatr Suppl. 2004 May;93(445):6-11. doi: 10.1111/j.1651-2227.2004.tb03048.x.


Children affected by advanced neuroblastoma have a discouraging prognosis, but intensive induction chemotherapy may increase the complete response rate. The combination of ifosfamide, carboplatin and etoposide (ICE) was used for the first time as front-line regimen in patients with stage 4 neuroblastoma over the age of 1 y. Similarly, second-line treatment for children with relapsed neuroblastoma, particularly after high-dose chemotherapy, has been unsatisfactory. The combination of topotecan and cyclophosphamide was studied in resistant or relapsed solid tumors. Furthermore, there is a need for effective palliative treatment in patients failing therapy. Temozolomide, a new dacarbazine analog with optimal oral bioavailability, is being used in an ongoing phase II study as an alternative to oral etoposide. Seventeen patients with stage 4 neuroblastoma have entered the ICE study; 15/16 (94%) major responses after induction were observed and 6/16 (37%) evaluable patients are disease free after a median of 51 mo. Twenty-one patients with relapsed/refractory disease (of whom 13 neuroblastomas) entered the topotecan/cyclophosphamide study: 7/21 (33%) patients responded. Forty-one patients entered the temozolomide study (of whom 16 had neuroblastomas): stable disease and symptom relief were obtained in 15/30 (50%) evaluable patients. Intensive induction with ICE resulted in a faster response with high response rate; a larger study with longer follow-up is needed to confirm a survival advantage. Second-line treatment was effective in obtaining remissions, some of them long lasting. Third-line treatment did not elicit measurable responses in neuroblastoma, but achieved prolonged freedom from disease progression and excellent palliation in several patients.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use*
  • Drug Resistance, Neoplasm
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Infant
  • Male
  • Neoplasm Recurrence, Local / drug therapy
  • Neuroblastoma / drug therapy*
  • Palliative Care
  • Temozolomide
  • Topotecan / administration & dosage
  • Treatment Outcome


  • Antineoplastic Agents, Alkylating
  • Etoposide
  • Dacarbazine
  • Topotecan
  • Cyclophosphamide
  • Carboplatin
  • Ifosfamide
  • Temozolomide