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

A. Donfrancesco, A. Jenkner, A. Castellano, I. Ilari, G. M. Milano, L. De Sio, R. Cozza, P. Fidani, G. Deb, C. De Laurentis, A. Inserra, C. Dominici

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)6-11
Number of pages6
JournalActa Paediatrica, International Journal of Paediatrics, Supplement
Volume93
Issue number445
Publication statusPublished - May 2004

Fingerprint

temozolomide
Topotecan
Ifosfamide
Carboplatin
Etoposide
Neuroblastoma
Cyclophosphamide
Therapeutics
Dacarbazine
Induction Chemotherapy

Keywords

  • ICE regimen
  • Neuroblastoma
  • Temozolomide
  • Topotecan

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

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title = "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",
abstract = "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.",
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author = "A. Donfrancesco and A. Jenkner and A. Castellano and I. Ilari and Milano, {G. M.} and {De Sio}, L. and R. Cozza and P. Fidani and G. Deb and {De Laurentis}, C. and A. Inserra and C. Dominici",
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T1 - 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

AU - Donfrancesco, A.

AU - Jenkner, A.

AU - Castellano, A.

AU - Ilari, I.

AU - Milano, G. M.

AU - De Sio, L.

AU - Cozza, R.

AU - Fidani, P.

AU - Deb, G.

AU - De Laurentis, C.

AU - Inserra, A.

AU - Dominici, C.

PY - 2004/5

Y1 - 2004/5

N2 - 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.

AB - 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.

KW - ICE regimen

KW - Neuroblastoma

KW - Temozolomide

KW - Topotecan

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