title: Phase I trial of 90Y-DOTATOC therapy in children and young adults with refractory solid tumors that express somatostatin receptors.
abstract: The purpose of this study was to conduct a phase I trial of (90)Y-DOTATOC to determine the dose-toxicity profile in children and young adults with somatostatin receptor-positive tumors.
  
  
  METHODS
  A 3 × 3 design was used to determine the highest tolerable dose of (90)Y-DOTATOC, with administered activities of 1.11, 1.48, and 1.85 GBq/m(2)/cycle given in 3 cycles at 6-wk intervals. An amino acid infusion was coadministered with the radiopharmaceutical for renal protection. Eligibility criteria included an age of 2-25 y, progressive disease, a positive lesion on (111)In-diethylenetriaminepentaacetic acid-D-Phe(1)-octreotide scanning, a glomerular filtration rate of 80 mL/min/1.73 m(2) or more, bone marrow cellularity of 40% or more or stored autologous hematopoietic stem cells, 60% or more on the Lansky Play Scale, and informed consent.
  
  
  RESULTS
  Seventeen subjects (age, 2-24 y) received at least 1 dose of (90)Y-DOTATOC; diagnoses included neuroblastoma, embryonal and astrocytic brain tumors, paraganglioma, multiple endocrine neoplasia IIB, and neuroendocrine tumors. No dose-limiting toxicities and no individual dose reductions due to renal or hematologic toxicity were noted. No complete responses were observed; 2 subjects experienced partial response, 5 had minor responses, 6 experienced stable disease, 2 had progressive disease, and 2 withdrew.
  
  
  CONCLUSIONS
  Peptide receptor radionuclide therapy with (90)Y-DOTATOC is safe in children and young adults and demonstrated a 12% partial response plus 29% minor response rate in patients with somatostatin receptor-positive tumors. No dose-limiting toxicities were observed. The recommended phase II dosing is 3 cycles of 1.85 GBq/m(2)/dose of (90)Y-DOTATOC coadministered with amino acids.
authors.affiliation: Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA. yusuf-menda@uiowa.edu
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Menda
authors.forename: M Sue
authors.initials: MS
authors.lastname: O'Dorisio
authors.forename: Simon
authors.initials: S
authors.lastname: Kao
authors.forename: Geetika
authors.initials: G
authors.lastname: Khanna
authors.forename: Stacy
authors.initials: S
authors.lastname: Michael
authors.forename: Mary
authors.initials: M
authors.lastname: Connolly
authors.forename: John
authors.initials: J
authors.lastname: Babich
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Dorisio
authors.forename: David
authors.initials: D
authors.lastname: Bushnell
authors.forename: Mark
authors.initials: M
authors.lastname: Madsen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000378:metabolism*; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C496730:90Y-octreotide, DOTA-Tyr(3)-; D015282:Octreotide