Masaki Chie, Sugino Kiminori, Saito Naoko, Saito Yoshiyuki, Tanaka Tomoaki, Ogimi Yuna, Maeda Tetsuyo, Osaku Tadatoshi, Akaishi Junko, Hames Kiyomi Y, Tomoda Chisato, Suzuki Akifumi, Matsuzu Kenichi, Uruno Takashi, Ohkuwa Keiko, Kitagawa Wataru, Nagahama Mitsuji, Takami Hiroshi, Ito Koichi
Department of Surgery, Ito Hospital, Tokyo, Japan.
Department of Diagnostic Radiology, Saitama Medical University, International Medical Center, Hidaka, Japan.
Endocr J. 2017 Aug 30;64(8):819-826. doi: 10.1507/endocrj.EJ17-0104. Epub 2017 Jul 28.
Although advanced thyroid carcinoma patients who cannot be cured by conventional therapy have lacked effective treatment, multitargeted tyrosine kinase inhibitors have recently become available. Phase 3 trials of lenvatinib showed a median time to objective response of 2 (95 % confidence interval (CI) 1.9-3.5) months, demonstrating that shrinks tumors rapidly. The phenomenon of immediate tumor shrink is known as early tumor shrinkage (ETS) which is related to clinical outcome in other malignancies. However, precisely when within 8 weeks lenvatinib starts to affect tumors remains unclear. In tumors near the carotid arteries, trachea, or esophagus, a rapid therapeutic effect can induce fistula formation or arterial bleeding. To prevent such treatment-emergent serious adverse events (SAE), early imaging evaluation seems to be very important. In this study, the point in time when lenvatinib started to shrink tumors was retrospectively investigated. The subjects were 16 patients who started lenvatinib administration between May and August 2015. Tumor size was evaluated by computed tomography (CT) scans frequently within the first 8 weeks according to the Response Evaluation Criteria In Solid Tumors (RECIST) guideline. Initial tumor response was defined as ≥ 10% tumor reduction. Serum thyroglobulin (Tg) level was monitored in 8 differentiated thyroid carcinoma (DTC) without TgAb patients. At the first evaluation, 13 patients (83.3 %) showed tumor reduction and that decreased with time. Thirteen patients (83.3 %) showed >10 % tumor reduction within 8 weeks. In all DTC patients, serum Tg level was markedly decreased. In conclusion, lenvatinib immediately shrinks tumors, the so-called ETS phenomenon. Therefore, careful attention should be paid to fistula formation from the early phase.
尽管无法通过传统疗法治愈的晚期甲状腺癌患者缺乏有效的治疗方法，但多靶点酪氨酸激酶抑制剂最近已开始应用。乐伐替尼的3期试验显示客观缓解的中位时间为2个月（95%置信区间[CI]1.9 - 3.5），表明其能迅速缩小肿瘤。肿瘤立即缩小的现象被称为早期肿瘤缩小（ETS），这与其他恶性肿瘤的临床结果相关。然而，乐伐替尼在8周内具体何时开始影响肿瘤仍不清楚。在靠近颈动脉、气管或食管的肿瘤中，快速的治疗效果可能会导致瘘管形成或动脉出血。为预防此类治疗中出现的严重不良事件（SAE），早期影像学评估似乎非常重要。在本研究中，对乐伐替尼开始缩小肿瘤的时间点进行了回顾性研究。研究对象为2015年5月至8月开始服用乐伐替尼的16例患者。根据实体瘤疗效评价标准（RECIST）指南，在最初的8周内频繁通过计算机断层扫描（CT）评估肿瘤大小。初始肿瘤反应定义为肿瘤缩小≥10%。对8例无TgAb的分化型甲状腺癌（DTC）患者监测血清甲状腺球蛋白（Tg）水平。在首次评估时，13例患者（83.3%）出现肿瘤缩小，且随时间推移缩小程度降低。13例患者（83.3%）在8周内肿瘤缩小>10%。在所有DTC患者中，血清Tg水平均显著降低。总之，乐伐替尼能立即缩小肿瘤，即所谓的ETS现象。因此，从早期阶段就应密切关注瘘管形成。
