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.
authors.affiliation: Division of Pediatric Oncology, Ospedale Pediatrico Bambino Gesù IRCCS, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Donfrancesco
authors.forename: A
authors.initials: A
authors.lastname: Jenkner
authors.forename: A
authors.initials: A
authors.lastname: Castellano
authors.forename: I
authors.initials: I
authors.lastname: Ilari
authors.forename: G M
authors.initials: GM
authors.lastname: Milano
authors.forename: L
authors.initials: L
authors.lastname: De Sio
authors.forename: R
authors.initials: R
authors.lastname: Cozza
authors.forename: P
authors.initials: P
authors.lastname: Fidani
authors.forename: G
authors.initials: G
authors.lastname: Deb
authors.forename: C
authors.initials: C
authors.lastname: De Laurentis
authors.forename: A
authors.initials: A
authors.lastname: Inserra
authors.forename: C
authors.initials: C
authors.lastname: Dominici
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009447:Neuroblastoma / Q000188:drug therapy*; D010166:Palliative Care; D000077204:Temozolomide; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D005047:Etoposide; D003606:Dacarbazine; D019772:Topotecan; D003520:Cyclophosphamide; D016190:Carboplatin; D007069:Ifosfamide; D000077204:Temozolomide