Gruber Joshua J, Colevas A Dimitrios
Stanford Cancer Center, Stanford University Medical Center, Stanford, California, USA.
Stanford Cancer Center, Stanford University Medical Center, Stanford, California, USA
Oncologist. 2015 Feb;20(2):113-26. doi: 10.1634/theoncologist.2014-0313. Epub 2015 Jan 23.
The treatment of differentiated thyroid cancer refractory to radioactive iodine (RAI) had been hampered by few effective therapies. Recently, tyrosine kinase inhibitors (TKIs) have shown activity in this disease. Clinical guidance on the use of these agents in RAI-refractory thyroid cancer is warranted.
Molecular mutations found in RAI-refractory thyroid cancer are summarized. Recent phase II and III clinical trial data for TKIs axitinib, lenvatinib, motesanib, pazopanib, sorafenib, sunitinib, and vandetinib are reviewed including efficacy and side effect profiles. Molecular targets and potencies of these agents are compared. Inhibitors of BRAF, mammalian target of rapamycin, and MEK are considered.
Routine testing for molecular alterations prior to therapy is not yet recommended. TKIs produce progression-free survival of approximately 1 year (range: 7.7-19.6 months) and partial response rates of up to 50% by Response Evaluation Criteria in Solid Tumors. Pazopanib and lenvatinib are the most active agents. The majority of patients experienced tumor shrinkage with TKIs. Common adverse toxicities affect dermatologic, gastrointestinal, and cardiovascular systems.
Multiple TKIs have activity in RAI-refractory differentiated thyroid cancer. Selection of a targeted agent should depend on disease trajectory, side effect profile, and goals of therapy.
放射性碘（RAI）难治性分化型甲状腺癌的治疗因有效疗法较少而受到阻碍。最近，酪氨酸激酶抑制剂（TKIs）在这种疾病中显示出活性。有必要对这些药物在RAI难治性甲状腺癌中的使用提供临床指导。
总结了RAI难治性甲状腺癌中发现的分子突变。回顾了TKIs阿昔替尼、乐伐替尼、莫替沙尼、帕唑帕尼、索拉非尼、舒尼替尼和凡德他尼的近期II期和III期临床试验数据，包括疗效和副作用情况。比较了这些药物的分子靶点和效力。考虑了BRAF、雷帕霉素哺乳动物靶点和MEK的抑制剂。
目前不建议在治疗前常规检测分子改变。根据实体瘤疗效评价标准，TKIs可使无进展生存期约为1年（范围：7.7 - 19.6个月），部分缓解率高达50%。帕唑帕尼和乐伐替尼是活性最强的药物。大多数患者使用TKIs后肿瘤缩小。常见的不良毒性影响皮肤、胃肠道和心血管系统。
多种TKIs在RAI难治性分化型甲状腺癌中具有活性。靶向药物的选择应取决于疾病进程、副作用情况和治疗目标。
