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 ⁹⁰Y-DOTATOC to determine the dose-toxicity profile in children and young adults with somatostatin receptor-positive tumors. Methods: A 3 x 3 design was used to determine the highest tolerable dose of ⁹⁰Y-DOTATOC, with administered activities of 1.11, 1.48, and 1.85 GBq/m²/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 ¹¹¹In-diethylenetriaminepentaacetic acid-D-Phe¹-octreotide scanning, a glomerular filtration rate of 80 mL/min/1.73 m² 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 ⁹⁰Y-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. Conclusion: Peptide receptor radionuclide therapy with ⁹⁰Y-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/m²/dose of ⁹⁰Y-DOTATOC coadministered with amino acids.