title: Phase I study of vincristine, irinotecan, and ¹³¹I-metaiodobenzylguanidine for patients with relapsed or refractory neuroblastoma: a new approaches to neuroblastoma therapy trial.
abstract: OBJECTIVE
  (131)I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical with activity in patients with relapsed or refractory neuroblastoma. Irinotecan is a known radiosensitizer with activity in neuroblastoma. This phase I study aimed to determine the recommended phase 2 dose of MIBG together with fixed doses of vincristine and irinotecan.
  
  
  METHODS
  Patients 1 to 30 years old with relapsed or refractory neuroblastoma and MIBG-avid tumors were eligible. All patients had autologous hematopoietic stem cells (PBSC) available and met standard phase I organ function requirements. Irinotecan (20 mg/m(2)/dose IV) was given on days 0 to 4 and 7 to 11, with vincristine (1.5 mg/m(2) IV) on days 0 and 7. MIBG was given on day 1 following a 3 + 3 phase I dose escalation design starting at 8 mCi/kg MIBG. PBSCs were administered at dose level 8 mCi/kg for prolonged myelosuppression and for all patients at 12 mCi/kg or more.
  
  
  RESULTS
  Twenty-four patients evaluable for dose escalation (median age, 6.7 years; range, 1.9-26.8 years) received 1 (n = 17), 2 (n = 5), or 3 (n = 2) cycles of therapy. Myelosuppression and diarrhea were the most common toxicities. Two of 6 patients at the 18 mCi/kg dose level had dose-limiting toxicity (DLT), including one with protocol-defined DLT with prolonged mild aspartate aminotransferase elevation. Eighteen mCi/kg was the recommended phase 2 dose. Six additional patients were treated at 18 mCi/kg, with one additional DLT. Responses (2 complete and 4 partial responses) occurred in 6 of 24 (25%) evaluable patients.
  
  
  CONCLUSIONS
  MIBG is tolerable and active at 18 mCi/kg with standard doses of vincristine and irinotecan.
authors.affiliation: Department of Pediatrics, UCSF School of Medicine, San Francisco, California 94143, USA. duboiss@peds.ucsf.edu
authors.forename: Steven G
authors.initials: SG
authors.lastname: DuBois
authors.forename: Louis
authors.initials: L
authors.lastname: Chesler
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.forename: Randall
authors.initials: R
authors.lastname: Hawkins
authors.forename: Fariba
authors.initials: F
authors.lastname: Goodarzian
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Greg
authors.initials: G
authors.lastname: Yanik
authors.forename: Michael
authors.initials: M
authors.lastname: Tagen
authors.forename: Clinton
authors.initials: C
authors.lastname: Stewart
authors.forename: Yael P
authors.initials: YP
authors.lastname: Mosse
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Denice
authors.initials: D
authors.lastname: Tsao-Wei
authors.forename: Araz
authors.initials: A
authors.lastname: Marachelian
authors.forename: Judith G
authors.initials: JG
authors.lastname: Villablanca
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
mesh_terms: D019797:3-Iodobenzylguanidine / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D009447:Neuroblastoma / Q000188:drug therapy*; D011379:Prognosis; D014018:Tissue Distribution; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D007457:Iodine Radioisotopes; D019797:3-Iodobenzylguanidine; D014750:Vincristine; D000077146:Irinotecan; D002166:Camptothecin