Role of vandetanib in the management of medullary thyroid cancer.
Role of vandetanib in the management of medullary thyroid cancer.
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Vandetanib在甲状腺癌管理中的作用。
DOI：
10.2147/btt.s24220
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Rondeau G
中科院分区：
文献类型：
--
作者：
Brassard M;Rondeau G
传统上可用的治疗，如细胞毒性化疗和外束放射治疗，是有限的，基本上是无效的转移性甲状腺髓样癌（MTC）。在过去的十年中，小分子酪氨酸激酶抑制剂（TKI）已被引入甲状腺癌领域，在各种其他肿瘤中显示有效。本文综述了凡德他尼（ZD 6474，Zactima™;阿斯利康）及其在MTC治疗中的作用。Vandetanib是一种口服TKI，靶向VEGF受体2和3，RET，以及更高浓度的表皮生长因子（EGF）受体。该药物已在两项重要的II期研究中进行了测试，证明100和300 mg/天剂量的凡德他尼对晚期MTC具有抗肿瘤活性。一项在331例局部晚期或转移性MTC患者中评价凡德他尼的III期试验（ZETA试验）显示，与安慰剂相比，接受凡德他尼治疗的患者PFS显著延长。所有研究中的毒性监测均报告了高不良反应发生率，患者最常见的不良反应为腹泻、皮疹、疲劳和恶心。凡德他尼目前在美国获批用于不可切除的局部晚期或转移性MTC，并已成为这种罕见和惰性病理的新标准治疗。
Traditionally available treatments, like cytotoxic chemotherapy and external-beam radiation therapy, are limited and essentially ineffective for metastatic medullary thyroid carcinoma (MTC). In the last decade, small-molecule tyrosine kinase inhibitors (TKI) have been introduced in the field of thyroid cancer, after having been shown effective in a wide variety of other tumors. This review focuses on vandetanib (ZD6474, Zactima™; AstraZeneca) and its role in the treatment of MTC. Vandetanib is an oral TKI that targets VEGF receptors 2 and 3, RET, and at higher concentrations, the epidermal growth factor (EGF) receptor. This drug has been tested in two important phase II studies which demonstrated that both the 100 and 300 mg/day dosage of vandetanib have antitumor activity on advanced MTC. A phase III trial (ZETA trial) evaluating vandetanib in 331 patients with locally advanced or metastatic MTC showed a significant prolongation of PFS for patients receiving vandetanib compared with placebo. Toxicity surveillance in all studies reported high rates of adverse effects with diarrhea, rash, fatigue and nausea being the most commonly experienced by patients. Vandetanib is currently approved in the United States for unresectable locally advanced or metastatic MTC and has become a new standard of care in this rare and indolent pathology.