Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study.
Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study.
复制标题
DOI：
10.1200/jco.2007.15.9566
复制
发表时间：
2008-10-10
期刊：
影响因子：
--
通讯作者：
Cohen RB
中科院分区：
文献类型：
--
作者：
Cohen EE;Rosen LS;Vokes EE;Kies MS;Forastiere AA;Worden FP;Kane MA;Sherman E;Kim S;Bycott P;Tortorici M;Shalinsky DR;Liau KF;Cohen RB
晚期、无法治愈的甲状腺癌患者不适合手术或放射性碘（131 I）治疗，几乎没有令人满意的治疗选择。这项多机构研究评估了阿昔替尼（一种口服、强效和选择性血管内皮生长因子受体（VEGFR）1、2和3抑制剂）在晚期甲状腺癌患者中的活性和安全性。对131 I耐药或不适合131 I治疗的任何组织学甲状腺癌患者入组一项单臂II期试验，接受阿昔替尼口服治疗（起始剂量，5 mg，每日两次）。根据实体瘤疗效评价标准，客观缓解率（ORR）为主要终点。次要终点包括缓解持续时间、无进展生存期（PFS）、总生存期、安全性和可溶性VEGFR的调节。入组了60例患者。在18例患者中观察到部分缓解，ORR为30%（95% CI，18.9 - 43.2）。另外23例患者（38%）报告了持续≥ 16周的疾病稳定。在所有组织学亚型中均观察到客观缓解。中位PFS为18.1个月（95% CI，12.1至无法估计）。阿昔替尼通常耐受良好，最常见的≥ 3级治疗相关不良事件为高血压（n = 7; 12%）。8名患者（13%）因不良事件而停止治疗。与sKIT相比，阿昔替尼选择性降低sVEGFR-2和sVEGFR-3血浆浓度，证明其靶向VEGFR。阿昔替尼是一种选择性VEGFR抑制剂，在所有组织学亚型的晚期甲状腺癌中具有引人注目的抗肿瘤活性。
Patients with advanced, incurable thyroid cancer not amenable to surgery or radioactive iodine (131I) therapy have few satisfactory therapeutic options. This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer. Patients with thyroid cancer of any histology that was resistant or not appropriate for 131I were enrolled onto a single-arm phase II trial to receive axitinib orally (starting dose, 5 mg twice daily). Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors was the primary end point. Secondary end points included duration of response, progression-free survival (PFS), overall survival, safety, and modulation of soluble (s) VEGFR. Sixty patients were enrolled. Partial responses were observed in 18 patients, yielding an ORR of 30% (95% CI, 18.9 to 43.2). Stable disease lasting ≥ 16 weeks was reported in another 23 patients (38%). Objective responses were noted in all histologic subtypes. Median PFS was 18.1 months (95% CI, 12.1 to not estimable). Axitinib was generally well tolerated, with the most common grade ≥ 3 treatment-related adverse event being hypertension (n = 7; 12%). Eight patients (13%) discontinued treatment because of adverse events. Axitinib selectively decreased sVEGFR-2 and sVEGFR-3 plasma concentrations versus sKIT, demonstrating its targeting of VEGFR. Axitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer.