Phase I trial of 90Y-DOTATOC therapy in children and young adults with refractory solid tumors that express somatostatin receptors.

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.
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.
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.
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.
AuthorsYusuf Menda, M Sue O'Dorisio, Simon Kao, Geetika Khanna, Stacy Michael, Mary Connolly, John Babich, Thomas O'Dorisio, David Bushnell, Mark Madsen
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 51 Issue 10 Pg. 1524-31 (Oct 2010) ISSN: 1535-5667 [Electronic] United States
PMID20847174 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • 90Y-octreotide, DOTA-Tyr(3)-
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • Octreotide
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Neoplasms (metabolism, radiotherapy)
  • Octreotide (adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
  • Radiation Injuries (diagnosis, etiology, metabolism)
  • Radiopharmaceuticals (adverse effects, pharmacokinetics, therapeutic use)
  • Receptors, Somatostatin (metabolism)
  • Risk Assessment
  • Young Adult

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