Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
J Nucl Med. 2010 Oct;51(10):1524-31. doi: 10.2967/jnumed.110.075226. Epub 2010 Sep 16.
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.
本研究的目的是进行一项 I 期临床试验，用（90）Y-DOTATOC 来确定儿童和青年患有生长抑素受体阳性肿瘤患者的剂量毒性概况。
采用 3×3 设计来确定（90）Y-DOTATOC 的最大耐受剂量，每 6 周给予 3 个周期，每个周期的给药活度分别为 1.11、1.48 和 1.85GBq/m²。放射性药物给药时同时给予氨基酸输液以保护肾脏。入选标准包括年龄 2-25 岁，疾病进展，111In-二乙三胺五乙酸-D-Phe1-奥曲肽扫描阳性病变，肾小球滤过率≥80mL/min/1.73m²或以上，骨髓细胞≥40%或储存自体造血干细胞， Lansky 游戏评分≥60%，并获得知情同意。
17 例（年龄 2-24 岁）患者至少接受了 1 次（90）Y-DOTATOC 治疗；诊断包括神经母细胞瘤、胚胎性和星形细胞瘤、副神经节瘤、多发性内分泌肿瘤 IIB 和神经内分泌肿瘤。未观察到剂量限制性毒性，也未因肾或血液毒性而减少任何个体剂量。未观察到完全缓解；2 例患者部分缓解，5 例患者有轻微缓解，6 例患者疾病稳定，2 例患者疾病进展，2 例患者退出。
用（90）Y-DOTATOC 进行肽受体放射性核素治疗在儿童和青年中是安全的，在患有生长抑素受体阳性肿瘤的患者中，观察到 12%的部分缓解率和 29%的轻微缓解率。未观察到剂量限制性毒性。推荐的 II 期剂量为 3 个周期，每个周期的（90）Y-DOTATOC 剂量为 1.85GBq/m²，同时给予氨基酸。
