Pepijn van Houten, James Nagarajah, Janneke E W Walraven, Martin Jaeger, Adriana C H van Engen-van Grunsven, Johannes W Smit, Romana T Netea-Maier
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引用次数: 0
Abstract
Objective: Patients with non-medullary thyroid carcinoma (NMTC) that are refractory to radioactive iodine (RAI) have a poor prognosis. Strategies for restoring the ability to take up iodine, so-called redifferentiation, are promising but not suitable for all patients. Preclinical studies, in human cell lines just as in a murine model, have shown that the cardiac glycoside digoxin restored RAI uptake. This prospective single-center open-label study aimed to investigate whether treatment with digoxin could reinduce clinically relevant RAI uptake in patients with metastasized RAI-refractory NMTC.
Methods: Eight patients with metastasized RAI-refractory NMTC were included between November 2022 and June 2023. Before treatment, a baseline [123I]NaI scintigraphy was performed. Thereafter, patients were treated with digoxin for 3 weeks. Starting doses depended on age and weight. For safety reasons, the usual therapeutic range was aimed for. After 1 week, the digoxin plasma concentration was measured, and the digoxin dose was adjusted if necessary. After 3 weeks of digoxin treatment, a second [123I]NaI scintigraphy was performed. RAI uptake was compared between the two scintigraphies.
Results: Seven patients completed the digoxin treatment and were evaluable. None of the seven patients showed clinically relevant RAI uptake after digoxin treatment. No digoxin-related serious adverse events occurred during this trial.
Conclusion: Contrary to results from preclinical trials, in this trial, 3 weeks of digoxin treatment did not reinduce RAI uptake in patients with NMTC. This highlights essential challenges regarding the approach toward optimization of studies aimed to restore the RAI uptake and its therapeutic efficacy through drug repurposing.
研究目的对放射性碘(RAI)难治的非髓性甲状腺癌(NMTC)患者预后较差。恢复摄取碘的能力(即所谓的再分化)的策略很有前景,但并非适用于所有患者。临床前研究表明,无论是在人类细胞系还是在小鼠模型中,强心甙地高辛都能恢复 RAI 的摄取。这项前瞻性单中心开放标签研究旨在探讨地高辛治疗是否能恢复转移性 RAI 难治性 NMTC 患者与临床相关的 RAI 摄取:在2022年11月至2023年6月期间,纳入了8名转移性RAI难治性NMTC患者。治疗前进行基线[123I]NaI-闪烁成像。此后,患者接受为期三周的地高辛治疗。起始剂量取决于年龄和体重。出于安全考虑,治疗剂量以通常的治疗范围为目标。一周后,测量地高辛血浆浓度,必要时调整地高辛剂量。地高辛治疗三周后,进行第二次[123I]NaI-闪烁成像。结果显示,7 名患者完成了地高辛治疗:结果:七名患者完成了地高辛治疗并接受了评估。结果:七名患者完成了地高辛治疗,并进行了评估。七名患者中没有一人在地高辛治疗后出现与临床相关的 RAI 摄取。试验期间未发生与地高辛相关的严重不良事件:结论:与临床前试验的结果相反,在这项试验中,三周的地高辛治疗并没有使 NMTC 患者重新摄取 RAI。这凸显了通过药物再利用来恢复 RAI 摄取及其疗效的优化研究方法所面临的重大挑战。
期刊介绍:
The ''European Thyroid Journal'' publishes papers reporting original research in basic, translational and clinical thyroidology. Original contributions cover all aspects of the field, from molecular and cellular biology to immunology and biochemistry, from physiology to pathology, and from pediatric to adult thyroid diseases with a special focus on thyroid cancer. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research. The journal will further publish formal guidelines in the field, produced and endorsed by the European Thyroid Association.