甲磺酸阿帕替尼治疗进展性碘难治性甲状腺癌的短期疗效及安全性初步报告

摘要

背景与目的：碘难治性甲状腺癌(radioactive iodine-refractory differentiated thyroid cancer，RAIR-DTC)是目前临床诊疗的难点与热点，目前国际指南中推荐的靶向治疗药物仅有索拉非尼及乐伐替尼。该研究报告具有我国自主知识产权的靶向药物甲磺酸阿帕替尼治疗进展性碘RAIR-DTC 8周后的短期疗效及安全性。方法：纳入10例进展性RAIR-DTC患者予阿帕替尼治疗(750 mg，每天1次，口服)。每2周复查甲状腺球蛋白(thyroglobulin，Tg)，每4周CT监测靶病灶(target lesions，TL)。观察甲状腺癌血清标志物Tg水平变化，采用实体瘤疗效评价标准1.1(response evaluation criteria in solid tumors，RECIST 1.1)评估疗效。初步评估患者经药物治疗的短期不良事件(adverse event，AE)以评估安全性。结果：8例Tg可评价的患者，在治疗2周后Tg即出现下降，在治疗8周后较基线平均降幅达68%，达到“生化部分缓解”。10例患者共18个TL，治疗4周后即出现缩小，在8周后较基线平均缩小达40％，9例患者(9/10，90%)达到部分缓解，1例(1/10，10%)呈疾病稳定，客观缓解率及疾病控制率分别达90%和100%。最常见的3级以上AE主要包括手足皮肤反应、高血压和低钙血症，分别占50%、30%和20%，未观察到与药物相关的严重AE。结论：甲磺酸阿帕替尼可安全用于RAIR-DTC治疗，且在8周治疗中从血清学及结构影像学角度证实快速有效，客观缓解率高。%Background and purpose:Radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) is a big challenge in the management of thyroid cancer. Sorafenib and lenvatinib are the 2 tyrosine kinase inhibitors (TKIs) recently approved by FDA, which could not be affordable for most of the Chinese patients. This pilot study aimed to evaluate the short term effcacy and safety of apatinib, a Chinese domestic TKI targeted vascular endothelial growth factor receptor (VEGFR), in advanced RAIR-DTC.Methods:Ten patients who were identiifed as progressive RAIR-DTC were enrolled in this study. Patients received oral apatinib 750 mg once daily. Both thyroglobulin (Tg) and/or Tg antibody (TgAb) levels were monitored every 2 weeks after the treatment. Computed tomography (CT) was per-formed every 4 weeks after apatinib treatment to evaluate the response according to response evaluation criteria in solid tumor version 1.1 (RECIST 1.1). Within 8 weeks after apatinib treatment, therapeutic response was evaluated in terms of Tg, a sensitive biochemical tumor marker for DTC, and RECIST 1.1 assessment. Meanwhile, the adverse events (AE) were monitored during the therapy.Results:The Tg levels declined after the ifrst 2 weeks of apatinib treatment, and a mean decline rate of 68% could be observed in 8 patients with Tg available for evaluation after 8 weeks, which repre-sented a biochemical partial response. Eighteen target lesions (TL) of 10 patients were evaluated and followed up. The diameter of TL began to decrease after 4 weeks, and a mean decline of 40% could be observed after 8 weeks’ apatinib treatment. A total of 9 patients (9/10) achieved partial response according to RECIST 1.1 criteria and 1 patient with stable disease, with 90% objective response rate and 100% disease control rate. The most common AE beyond grade 3 included hand-foot-skin reactions, hypertension and hypocalcemia, which accounted for 50%, 30% and 20% of the cases, respectively. No severe AE related to apatinib was observed during the treatment.Conclusion:A safe and rapid response and high partial response rate in terms of biochemistry, RECIST 1.1 could be observed in RAIR-DTC patients within 8 weeks of apatinib treatment.