title: Randomized Trial of prophylactic granulocyte colony-stimulating factor during rapid COJEC induction in pediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study.
abstract: OBJECTIVE
  To reduce the incidence of febrile neutropenia during rapid COJEC (cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide given in a rapid delivery schedule) induction. In the High-Risk Neuroblastoma-1 (HR-NBL1) trial, the International Society of Paediatric Oncology European Neuroblastoma Group (SIOPEN) randomly assigned patients to primary prophylactic (PP) versus symptom-triggered granulocyte colony-stimulating factor (GCSF; filgrastim).
  
  
  METHODS
  From May 2002 to November 2005, 239 patients in 16 countries were randomly assigned to receive or not receive PPGCSF. There were 144 boys with a median age of 3.1 years (range, 1 to 17 years) of whom 217 had International Neuroblastoma Staging System (INSS) stage 4 and 22 had stage 2 or 3 MYCN-amplified disease. The prophylactic arm received a single daily dose of 5 microg/kg GCSF, starting after each of the eight COJEC chemotherapy cycles and stopping 24 hours before the next cycle. Chemotherapy was administered every 10 days regardless of hematologic recovery, provided that infection was controlled.
  
  
  RESULTS
  The PPGCSF arm had significantly fewer febrile neutropenic episodes (P = .002), days with fever (P = .004), hospital days (P = .017), and antibiotic days (P = .001). Reported Common Toxicity Criteria (CTC) graded toxicity was also significantly reduced: infections per cycle (P = .002), fever (P < .001), severe leucopenia (P < .001), neutropenia (P < .001), mucositis (P = .002), nausea/vomiting (P = .045), and constipation (P = .008). Severe weight loss was reduced significantly by 50% (P = .013). Protocol compliance with the rapid induction schedule was also significantly better in the PPGCSF arm shown by shorter time to completion (P = .005). PPGCSF did not adversely affect response rates or success of peripheral-blood stem-cell harvest.
  
  
  CONCLUSIONS
  Following these results, PPG-GSF was advised for all patients on rapid COJEC induction.
authors.affiliation: St Anna Children's Hospital, Kinderspitalgasse 6, Vienna, Austria. ruth.ladenstein@ccri.at
authors.forename: Ruth
authors.initials: R
authors.lastname: Ladenstein
authors.forename: Dominique
authors.initials: D
authors.lastname: Valteau-Couanet
authors.forename: Penelope
authors.initials: P
authors.lastname: Brock
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
authors.forename: Victoria
authors.initials: V
authors.lastname: Castel
authors.forename: Geneviève
authors.initials: G
authors.lastname: Laureys
authors.forename: Josef
authors.initials: J
authors.lastname: Malis
authors.forename: Vassilios
authors.initials: V
authors.lastname: Papadakis
authors.forename: Ana
authors.initials: A
authors.lastname: Lacerda
authors.forename: Ellen
authors.initials: E
authors.lastname: Ruud
authors.forename: Per
authors.initials: P
authors.lastname: Kogner
authors.forename: Miklos
authors.initials: M
authors.lastname: Garami
authors.forename: Walentyna
authors.initials: W
authors.lastname: Balwierz
authors.forename: Henrik
authors.initials: H
authors.lastname: Schroeder
authors.forename: Maja
authors.initials: M
authors.lastname: Beck-Popovic
authors.forename: Günter
authors.initials: G
authors.lastname: Schreier
authors.forename: David
authors.initials: D
authors.lastname: Machin
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pötschger
authors.forename: Andrew
authors.initials: A
authors.lastname: Pearson
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy* / Q000523:psychology; D011788:Quality of Life; D012306:Risk
chemical_list: D016179:Granulocyte Colony-Stimulating Factor