title: Outcome of children with relapsed or refractory neuroblastoma: A meta-analysis of ITCC/SIOPEN European phase II clinical trials.
abstract: Few randomized trials have been conducted in children with relapsed/refractory neuroblastoma and data about outcomes including progression-free survival (PFS) in these patients are scarce.
  
  
  
  A meta-analysis of three phase II studies of children with relapsed/refractory neuroblastoma conducted in Europe (temozolomide, topotecan-vincristine-doxorubicin and topotecan-temozolomide) was performed. Individual patient data with extended follow-up were collected from the trial databases after publication to describe trial outcomes (response rate, clinical benefit ratio, duration of treatment, PFS, and overall survival [OS]). Characteristics of subjects with relapsed/refractory neuroblastoma were compared.
  
  
  
  Data from 71 children and adolescents with relapsed/refractory neuroblastoma were collected. Response definitions were not homogeneous in the three trials. Patients were on study for a median of 3.5 months (interquartile range [IQR] 1.9-6.2). Of those, 35.2% achieved a complete or partial response, 26.3% experienced a response after more than two cycles, and 23.9% received more than six cycles. Median PFS from study entry for all, refractory, and relapsed patients was 6.4 ± 1.0, 12.5 ± 6.8, and 5.7 ± 1.0 months, respectively (P = 0.006). Median OS from study entry for all, refractory, and relapsed patients was 16.1 ± 4.3, 27.9 ± 20.2, and 11.0 ± 1.6 months, respectively (P = 0.03).
  
  
  
  Baseline data for response rate, clinical benefit ratio, duration of treatment, PFS, and OS were provided. Two subpopulations (relapsed/refractory) were clearly distinct and should be included in the interpretation of all trials. These results should help informing the design of forthcoming studies in relapsed/refractory neuroblastoma.
authors.affiliation: HNJ-CNIO Clinical Research Unit, Hospital Universitario Niño Jesus, Madrid, Spain.
authors.forename: Lucas
authors.initials: L
authors.lastname: Moreno
authors.affiliation: Hôpital des Enfants, CHU, Toulouse, France.
authors.forename: Herve
authors.initials: H
authors.lastname: Rubie
authors.affiliation: HNJ-CNIO Clinical Research Unit, Hospital Universitario Niño Jesus, Madrid, Spain.
authors.forename: Amalia
authors.initials: A
authors.lastname: Varo
authors.affiliation: Universite Paris-Saclay, Univ. Paris-Sud, CESP, INSERM, Gustave Roussy, Villejuif, France.
authors.forename: Marie Cecile
authors.initials: MC
authors.lastname: Le Deley
authors.affiliation: Biostatistics Unit, Gustave Roussy, Villejuif, France.
authors.forename: Loredana
authors.initials: L
authors.lastname: Amoroso
authors.affiliation: Biostatistics Unit, Gustave Roussy, Villejuif, France.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Chevance
authors.affiliation: Department of Pediatric Hemato-Oncology, Istituto Gianina, Gaslini, Genova.
authors.forename: Alberto
authors.initials: A
authors.lastname: Garaventa
authors.affiliation: Hôpital des Enfants, CHU, Toulouse, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Gambart
authors.affiliation: HNJ-CNIO Clinical Research Unit, Hospital Universitario Niño Jesus, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Bautista
authors.affiliation: Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Valteau-Couanet
authors.affiliation: Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Birgit
authors.initials: B
authors.lastname: Geoerger
authors.affiliation: Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Vassal
authors.affiliation: Biostatistics Unit, Gustave Roussy, Villejuif, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Paoletti
authors.affiliation: Institute of Cancer Research, London, UK.
authors.forename: Andrew D J
authors.initials: AD
authors.lastname: Pearson
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D017322:Clinical Trials, Phase II as Topic; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005060:Europe; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate; D000077204:Temozolomide; D019772:Topotecan / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D003606:Dacarbazine; D019772:Topotecan; D004317:Doxorubicin; D000077204:Temozolomide
keywords: neuroblastoma; phase II; refractory; relapse; temozolomide; topotecan