title: Upfront treatment of high-risk neuroblastoma with a combination of 131I-MIBG and topotecan.
abstract: BACKGROUND
  (131)I-metaiodobenzylguanidine ((131) I-MIBG) has a significant anti-tumor effect against neuroblastoma (NBL). Topotecan (TPT) can act as a radio-sensitizer and can up-regulate (131) I-MIBG uptake in vitro in NBL.
  
  
  OBJECTIVE
  Determine the efficacy of the combination of (131) I-MIBG with topotecan in newly diagnosed high-risk (HR) NBL patients.
  
  
  METHODS
  In a prospective, window phase II study, patients with newly diagnosed high-risk neuroblastoma were treated at diagnosis with two courses of (131) I-MIBG directly followed by topotecan (0.7 mg/m(2) for 5 days). After these two courses, standard induction treatment (four courses of VECI), surgery and myeloablative therapy (MAT) with autologous stem cell transplantation (ASCT) was given. Response was measured after two courses of (131) I-MIBG-topotecan and post MAT and ASCT. Hematologic toxicity and harvesting of stem cells were analysed. Topoisomerase-1 activity levels were analysed in primary tumor material.
  
  
  RESULTS
  Sixteen patients were included in the study; median age was 2.8 years. MIBG administered activity (AA) (median and range) of the first course was 0.5 (0.4-0.6) GBq/kg (giga Becquerel/kilogram) and of the second course 0.4 (0.3-0.5) GBq/kg. The overall objective response rate (ORR) after 2 × MIBG/TPT was 57%, the primary tumor RR was 94%, and bone marrow RR was 43%. The ORR post MAT and ASCT was 57%. Hematologic grade four toxicity: after first and second (131) I-MIBG (platelets 25/33%, neutrophils 13/33%, and hemoglobin 25/7%). Topoisomerase-1 activity levels were increased in 10/10 (100%) measured tumors.
  
  
  CONCLUSIONS
  Combination therapy with MIBG-topotecan is an effective window treatment in newly diagnosed high-risk neuroblastoma patients.
authors.affiliation: Department of Pediatric Oncology, Amsterdam Medical Centre (AMC), Amsterdam, the Netherlands.|Princess Máxima Centre for Pediatric Oncology, Utrecht, the Netherlands.
authors.forename: Kathelijne C J M
authors.initials: KC
authors.lastname: Kraal
authors.affiliation: Department of Pediatric Oncology, Amsterdam Medical Centre (AMC), Amsterdam, the Netherlands.
authors.forename: Godelieve A M
authors.initials: GA
authors.lastname: Tytgat
authors.affiliation: Department of Nuclear Medicine, Amsterdam Medical Centre (AMC), Amsterdam, the Netherlands.
authors.forename: Berthe L F
authors.initials: BL
authors.lastname: van Eck-Smit
authors.affiliation: Department of Nuclear Medicine, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Boen
authors.initials: B
authors.lastname: Kam
authors.affiliation: Department of Pediatric Oncology, Amsterdam Medical Centre (AMC), Amsterdam, the Netherlands.
authors.forename: Huib N
authors.initials: HN
authors.lastname: Caron
authors.affiliation: Princess Máxima Centre for Pediatric Oncology, Utrecht, the Netherlands.|Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: van Noesel
mesh_terms: D019797:3-Iodobenzylguanidine / Q000008:administration & dosage; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D064592:Autografts; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009447:Neuroblastoma / Q000401:mortality / Q000628:therapy*; D011446:Prospective Studies; D012307:Risk Factors; D033581:Stem Cell Transplantation; D019772:Topotecan / Q000008:administration & dosage; D019172:Transplantation Conditioning
chemical_list: D019797:3-Iodobenzylguanidine; D019772:Topotecan
keywords: meta-iodobenzylguanidine (MIBG); neuroblastoma (NBL); topotecan (TPT)