RADTHYR：一项开放标签、单臂、前瞻性多中心 II 期临床试验，评估镭-223 治疗放射性碘难治性分化型甲状腺癌骨转移。
RADTHYR: an open-label, single-arm, prospective multicenter phase II trial of Radium-223 for the treatment of bone metastases from radioactive iodine refractory differentiated thyroid cancer.
机构信息
Nuclear Medicine and Endocrine Oncology, Gustave Roussy and Paris Saclay University, 114 Rue Edouard Vaillant, Villejuif, France.
Department of Medical Sciences, University of Turin, Corso Dogliotti, 14, 10126, Torino, Italy.
出版信息
Eur J Nucl Med Mol Imaging. 2021 Sep;48(10):3238-3249. doi: 10.1007/s00259-021-05229-y. Epub 2021 Feb 23.
PURPOSE
This is the first prospective trial evaluating the efficacy of alpha emitter Radium-223 in patients with bone metastases from radioactive iodine (RAI) refractory (RAIR) differentiated thyroid cancer.
METHODS
RADTHYR is a multicenter, single-arm prospective Simon two-stage phase II trial (NCT02390934). The primary objective was to establish the efficacy of three administrations of 55 kBq/kg of Radium-223 by F-FDG PET/CT according to PERCIST criteria. Secondary objectives were to establish the efficacy of six administrations of Radium-223 by F-FDG PET/CT, Tc-HMDP bone scan and FNa PET/CT, clinical benefits, changes in serum bone markers, thyroglobulin levels, and safety.
RESULTS
Ten patients were enrolled between July 2015 and December 2017 (4 M; median age 74 years). Prior to Radium-223 administration, patients received a median RAI cumulative activity of 15 GBq (7.4-35.6), external radiation therapy (n = 9), bone surgery (n = 8), cimentoplasty (n = 5), and cryoablation (n = 2). F-FDG PET/CT showed stable disease (SD) in 4/10 and progressive disease (PD) in 6/10 cases after three administrations and SD in 4/10, PD in 5/10 cases, and 1/10 non-evaluable (NE) case after six administrations. After six injections, Tc-HMDP bone scan showed SD in 9 cases and was NE in 1 case; FNa PET/CT showed SD in 8 cases, partial response (PR) in 1 case, and was NE in 1 case. No significant clinical benefits were reported during the study. A skeletal event occurred in 6 patients (median time without skeletal event of 12.1 months). Seventy-seven adverse events were reported during treatment (7 of grade 3-4). Three patients developed an acute myeloid, a promyelocytic, and a chronic myeloid leukemia after the last Radium-223 administration considered as drug-related.
CONCLUSION
The trial was stopped after interim analysis for lack of response of bone metastases from RAIR thyroid cancer to Radium-223. Severe hematological toxicity was observed in patients heavily pretreated with RAI and external radiation.
TRIAL REGISTRATION NUMBER
NCT02390934. Registration date 18.03.2015.
目的
这是第一项评估α发射体镭-223 治疗放射性碘（RAI）难治性（RAIR）分化型甲状腺癌骨转移患者疗效的前瞻性试验。
方法
RADTHYR 是一项多中心、单臂前瞻性 Simon 两阶段 II 期试验（NCT02390934）。主要目的是根据 PERCIST 标准确定三次 55kBq/kg 镭-223 给药的疗效。次要目的是确定六次镭-223 给药的疗效，包括 F-FDG PET/CT、Tc-HMDP 骨扫描和 FNa PET/CT，临床获益，血清骨标志物、甲状腺球蛋白水平的变化，以及安全性。
结果
2015 年 7 月至 2017 年 12 月期间，共纳入 10 名患者（4 名男性；中位年龄 74 岁）。在接受镭-223 治疗前，患者接受了中位 RAI 累积活度 15GBq（7.4-35.6），外照射治疗（n=9）、骨手术（n=8）、骨水泥成形术（n=5）和冷冻消融术（n=2）。三次给药后，F-FDG PET/CT 显示 4/10 例为疾病稳定（SD），6/10 例为疾病进展（PD）；六次给药后，4/10 例为 SD，5/10 例为 PD，1/10 例为不可评估（NE）。六次注射后，Tc-HMDP 骨扫描显示 9 例为 SD，1 例为 NE；FNa PET/CT 显示 8 例为 SD，1 例为部分缓解（PR），1 例为 NE。研究期间未报告明显的临床获益。6 名患者发生骨骼事件（无骨骼事件的中位时间为 12.1 个月）。治疗期间共报告 77 例不良事件（3-4 级 7 例）。最后一次镭-223 给药后，3 名患者发生急性髓系白血病、早幼粒细胞白血病和慢性髓系白血病，认为与药物有关。
结论
由于 RAI 难治性甲状腺癌骨转移对镭-223 无反应，试验在中期分析后停止。在 RAI 和外照射治疗的大量预处理患者中观察到严重的血液学毒性。
试验注册号
NCT02390934。注册日期：2015 年 3 月 18 日。
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