Sherman Steven I, Wirth Lori J, Droz Jean-Pierre, Hofmann Michael, Bastholt Lars, Martins Renato G, Licitra Lisa, Eschenberg Michael J, Sun Yu-Nien, Juan Todd, Stepan Daniel E, Schlumberger Martin J
Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, Houston 77230-1402, USA.
N Engl J Med. 2008 Jul 3;359(1):31-42. doi: 10.1056/NEJMoa075853.
The expression of vascular endothelial growth factor (VEGF) is characteristic of differentiated thyroid cancer and is associated with aggressive tumor behavior and a poor clinical outcome. Motesanib diphosphate (AMG 706) is a novel oral inhibitor of VEGF receptors, platelet-derived growth-factor receptor, and KIT.
In an open-label, single-group, phase 2 study, we treated 93 patients who had progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer with 125 mg of motesanib diphosphate, administered orally once daily. The primary end point was an objective response as assessed by an independent radiographic review. Additional end points included the duration of the response, progression-free survival, safety, and changes in serum thyroglobulin concentration.
Of the 93 patients, 57 (61%) had papillary thyroid carcinoma. The objective response rate was 14%. Stable disease was achieved in 67% of the patients, and stable disease was maintained for 24 weeks or longer in 35%; 8% had progressive disease as the best response. The Kaplan-Meier estimate of the median duration of the response was 32 weeks (the lower limit of the 95% confidence interval [CI] was 24; the upper limit could not be estimated because of an insufficient number of events); the estimate of median progression-free survival was 40 weeks (95% CI, 32 to 50). Among the 75 patients in whom thyroglobulin analysis was performed, 81% had decreased serum thyroglobulin concentrations during treatment, as compared with baseline levels. The most common treatment-related adverse events were diarrhea (in 59% of the patients), hypertension (56%), fatigue (46%), and weight loss (40%).
Motesanib diphosphate can induce partial responses in patients with advanced or metastatic differentiated thyroid cancer that is progressive. (ClinicalTrials.gov number, NCT00121628.)
血管内皮生长因子（VEGF）的表达是分化型甲状腺癌的特征，与肿瘤侵袭性及不良临床预后相关。二磷酸莫替沙尼（AMG 706）是一种新型口服VEGF受体、血小板衍生生长因子受体及KIT抑制剂。
在一项开放标签、单组、2期研究中，我们对93例进展期、局部晚期或转移性、放射性碘难治性分化型甲状腺癌患者给予125 mg二磷酸莫替沙尼口服，每日1次。主要终点为由独立影像学检查评估的客观缓解。其他终点包括缓解持续时间、无进展生存期、安全性及血清甲状腺球蛋白浓度变化。
93例患者中，57例（61%）为乳头状甲状腺癌。客观缓解率为14%。67%的患者病情稳定，35%的患者病情稳定持续24周或更长时间；8%的患者最佳反应为疾病进展。根据Kaplan-Meier法估计，缓解的中位持续时间为32周（95%置信区间下限为24周；由于事件数量不足，上限无法估计）；中位无进展生存期估计为40周（95%置信区间为32至50周）。在进行甲状腺球蛋白分析的75例患者中，81%的患者治疗期间血清甲状腺球蛋白浓度较基线水平下降。最常见的治疗相关不良事件为腹泻（59%的患者）、高血压（56%）、疲劳（46%）及体重减轻（40%）。
二磷酸莫替沙尼可使进展期或转移性分化型甲状腺癌患者产生部分缓解。（临床试验注册号：NCT00121628）
