Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Via S. Pansini 5, Naples, Italy.
Clin Endocrinol (Oxf). 2013 May;78(5):760-7. doi: 10.1111/cen.12057.
Radioactive iodine is a crucial tool for treatment of differentiated thyroid cancer (DTC). In 5% of cases, DTCs lose I-131 avidity and assume an aggressive behaviour. Treatment options for iodine-refractory DTC are limited. We report the experience of off-label use of the tyrosine kinase inhibitor sorafenib for treatment of advanced iodine-refractory DTC.
Patients with progressive DTC refractory to radioactive iodine were treated with sorafenib used off-label independently from their performance status. Primary study end-points were radiological response, progression-free survival (PFS) and safety. Secondary end-points were site-specific radiological response and overall survival (OS). An exploratory analysis of the role of serum thyroglobulin (Tg) and fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed.
A total of 17 patients were included in the study. Median follow-up was 15·5 months. Clinical benefit was obtained in 71% of subjects (30% partial response and 41% stable disease). Sorafenib was mostly well tolerated, but a high incidence of fatal events was reported (three patients died from severe bleeding events and two from cardiac arrest). Median PFS was 9 months. Median OS was 10 months. The best responses were observed in lymph nodes and lung. Baseline Tg levels and the Tg response to treatment were correlated to both radiological response and PFS. Baseline FDG-PET assessment and early FDG-PET response were correlated to radiological response.
Sorafenib allows morphological disease control in the majority of patients with iodine-refractory DTC. Progression-free survival and overall survival were lower than in previous studies as a consequence of the worse clinical condition of our patients. Sorafenib is mostly well tolerated but could have been responsible for the reported fatal events. Baseline Tg and the Tg response to treatment could be useful for predicting morphological response and clinical outcome. Early FDG-PET response could be helpful for the timely identification of nonresponding patients.
放射性碘是治疗分化型甲状腺癌（DTC）的重要手段。在 5%的病例中，DTC 失去了对碘-131 的摄取能力，表现出侵袭性的行为。对于碘难治性 DTC 的治疗选择有限。我们报告了使用酪氨酸激酶抑制剂索拉非尼治疗晚期碘难治性 DTC 的经验。
对放射性碘治疗无效的进展性 DTC 患者，使用索拉非尼进行标签外治疗，不考虑其功能状态。主要研究终点为影像学反应、无进展生存期（PFS）和安全性。次要终点为特定部位的影像学反应和总生存期（OS）。对血清甲状腺球蛋白（Tg）和氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）进行了探索性分析。
共纳入 17 例患者。中位随访时间为 15.5 个月。71%的患者获得临床获益（30%部分缓解，41%疾病稳定）。索拉非尼大多耐受性良好，但报告了较高的致死性事件发生率（3 例死于严重出血事件，2 例死于心脏骤停）。中位 PFS 为 9 个月。中位 OS 为 10 个月。淋巴结和肺部的最佳反应。基线 Tg 水平和治疗后的 Tg 反应与影像学反应和 PFS 相关。基线 FDG-PET 评估和早期 FDG-PET 反应与影像学反应相关。
索拉非尼可使大多数碘难治性 DTC 患者的形态学疾病得到控制。无进展生存期和总生存期均低于既往研究，这与我们患者的临床状况较差有关。索拉非尼大多耐受性良好，但可能是报告的致死性事件的原因。基线 Tg 和治疗后的 Tg 反应可用于预测形态学反应和临床结局。早期 FDG-PET 反应有助于及时识别无反应患者。
