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

• Published in: The Journal of nuclear medicine (1978) Vol. 51; no. 10; p. 1524
• Main Authors: Menda, Yusuf, O'Dorisio, M Sue, Kao, Simon, Khanna, Geetika, Michael, Stacy, Connolly, Mary, Babich, John, O'Dorisio, Thomas, Bushnell, David, Madsen, Mark
• Format: Journal Article
• Language: English
• Published: United States 01.10.2010
• Subjects: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Maximum Tolerated Dose; Neoplasms - metabolism; Neoplasms - radiotherapy; Octreotide - adverse effects; Octreotide - analogs & derivatives; Octreotide - pharmacokinetics; Octreotide - therapeutic use; Radiation Injuries - diagnosis; Radiation Injuries - etiology; Radiation Injuries - metabolism; Radiopharmaceuticals - adverse effects; Radiopharmaceuticals - pharmacokinetics; Radiopharmaceuticals - therapeutic use; Receptors, Somatostatin - metabolism; Risk Assessment; Young Adult
• ISSN: 1535-5667; 1535-5667
• DOI: 10.2967/jnumed.110.075226

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.