title: Chemotherapy for patients with recurrent or refractory neuroblastoma: a POG Phase II study.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the efficacy and toxicity of three different salvage regimens (Rx) in children with recurrent or refractory neuroblastoma.
  
  
  METHODS
  Forty-six children with recurrent or refractory neuroblastoma received treatment according to one of three regimens: Rx 1 (five patients), high-dose cisplatin (HDP) (200 mg/m2) with concurrent sodium thiosulfate (STS) (9.9 g/m2) as a nephroprotectant and etoposide (VP-16) (200 mg/m2/day for 3 days); Rx 2 (22 patients), high-dose carboplatin (HD-CBDCA) (500 mg/m2/day for 2 days) and VP-16 (100 mg/m2/day for 3 days); Rx 3 (19 patients), ifosfamide (1.5 g/m2/day for 3 days) followed by CBDCA (400 mg/m2) on day 4. Chemotherapy was administered every 3-4 weeks. Responses were assessed following four courses with or without surgery. Patients achieving less than a partial response (PR) on their primary treatment were crossed over to the next regimen (i.e., Rx 1 --> Rx 2 <--> Rx 3).
  
  
  RESULTS
  Rx 1 was ended early owing to grade 4 nephrotoxicity in two patients following their first course. Ten of 22 evaluated patients (45%) primarily (n = 19) or secondarily (n = 3) treated by Rx 2 responded [five complete response (CR) and five PRs]. Nine of the 23 evaluated patients (39%) on Rx 3 as primary (n = 18) or secondary (n = 5) treatment responded (one CR and eight PRs). Grades 3-4 neutropenia and thrombocytopenia occurred after 80% and 50% of courses administered on Rx 2 and Rx 3, respectively. Central venous line infections were the most commonly documented infections on these regimens.
  
  
  CONCLUSIONS
  Rx 2 and Rx 3 are active combinations in patients with recurrent or refractory neuroblastoma and are associated with manageable toxicity. HDP administered as a short i.v. infusion with concurrent STS infusion cannot be safely given to children with neuroblastoma pretreated with cisplatin.
authors.affiliation: Department of Pediatrics, Hematology/Oncology/BMT, Emory University School of Medicine, Atlanta, Georgia 30322, U.S.A.
authors.forename: C S
authors.initials: CS
authors.lastname: Alvarado
authors.forename: C
authors.initials: C
authors.lastname: Kretschmar
authors.forename: V V
authors.initials: VV
authors.lastname: Joshi
authors.forename: S
authors.initials: S
authors.lastname: Toledano
authors.forename: A
authors.initials: A
authors.lastname: Cantor
authors.forename: D
authors.initials: D
authors.lastname: Strother
authors.forename: R
authors.initials: R
authors.lastname: Nitschke
authors.forename: R P
authors.initials: RP
authors.lastname: Castleberry
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D012008:Recurrence; D016896:Treatment Outcome