title: Phase I/II study of (131)I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma.
abstract: BACKGROUND
  (131)I-metaiodobenzylguanidine (MIBG) is an active radiopharmaceutical in neuroblastoma. A previous study demonstrated that MIBG could be combined with vincristine and prolonged irinotecan, although 25% of first courses had grade 3 diarrhoea. The current phase I/II study evaluated MIBG with vincristine and 5 days of higher-dose irinotecan.
  
  
  METHODS
  Patients 1-30 years old with advanced neuroblastoma were eligible. Patients received cefixime on days -1 to +6, irinotecan (50 mg m(-2) per dose IV) on days 0-4, vincristine (2 mg m(-2)) on day 0, MIBG (555 or 666 MBq kg(-1)) on day 1, and peripheral blood stem cells on day 13. UGT1A1 genotyping was performed in consenting patients.
  
  
  RESULTS
  Thirty-two patients (12 phase I ; 20 phase II) received 42 courses. No dose-limiting toxicities were seen during dose escalation and the recommended administered activity was 666 MBq kg(-1). Myelosuppression and diarrhoea were the most common toxicities, with grade 3 diarrhoea in 6% of first courses. Patients homozygous for UGT1A1*28 had more grade 4 thrombocytopenia (80% vs 37%; P=0.14). Responses (five complete and four partial) occurred in 9 out of 32 (28%) patients.
  
  
  CONCLUSIONS
  MIBG (666 MBq kg(-1)) with vincristine and this irinotecan schedule is tolerable and active, with less severe diarrhoea compared with a regimen using more protracted irinotecan.
authors.affiliation: Department of Pediatrics, UCSF School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA 94143, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: DuBois
authors.affiliation: Department of Pediatrics, UCSF School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA 94143, USA.
authors.forename: S
authors.initials: S
authors.lastname: Allen
authors.affiliation: Department of Pediatrics, UCSF School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA 94143, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bent
authors.affiliation: Department of Epidemiology and Biostatistics, UCSF School of Medicine, San Francisco, CA 94143, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Hilton
authors.affiliation: Department of Pediatrics, UCSF School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA 94143, USA.
authors.forename: F
authors.initials: F
authors.lastname: Hollinger
authors.affiliation: Department of Radiology, UCSF School of Medicine, San Francisco, CA 94143, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hawkins
authors.affiliation: Department of Radiology, UCSF School of Medicine, San Francisco, CA 94143, USA.
authors.forename: J
authors.initials: J
authors.lastname: Courtier
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine and Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Y P
authors.initials: YP
authors.lastname: Mosse
authors.affiliation: Department of Pediatrics, UCSF School of Medicine, UCSF Benioff Children's Hospital, San Francisco, CA 94143, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Matthay
mesh_terms: D019797:3-Iodobenzylguanidine / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D059248:Chemoradiotherapy; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D009447:Neuroblastoma / Q000235:genetics / Q000628:therapy*; D011879:Radiotherapy Dosage; D014750:Vincristine / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D007457:Iodine Radioisotopes; D019797:3-Iodobenzylguanidine; D014750:Vincristine; D000077146:Irinotecan; D002166:Camptothecin