Kim Christina A K, Price-Hiller Julie, Chu Quincy S, Tankel Keith, Hennig Ron, Sawyer Michael B, Spratlin Jennifer L
Cross Cancer Institute, 11560 University Avenue NW, Edmonton, AB, T6G 1Z2, Canada,
Invest New Drugs. 2014 Oct;32(5):1036-45. doi: 10.1007/s10637-014-0113-6. Epub 2014 May 23.
Reversible posterior leukoenecphalopathy syndrome (RPLS) is a rare clinicoradiologic syndrome characterized by neurologic symptoms such as seizures, headaches, visual abnormalities, confusion and encephalopathy, accompanied by vasogenic edema of posterior white matter seen on neuroimaging. It has been reported in association with many anti-angiogenic therapies, including bevacizumab, sunitinib, sorafenib, pazopanib and regorafenib. Cediranib is a potent, orally available small molecule tyrosine kinase inhibitor with anti-angiogenic activity, which has been shown to have activity against various solid tumors.
We present a case of a 65 year old male with metastatic adenocarcinoma of the rectum who received cediranib as part of a phase I clinical trial. He developed confusion and fluctuations in his level of consciousness. MRI of the brain revealed diffuse low level T2 signal abnormality in the cerebral peduncles, pons, and medulla and patchy T2 signal in both thalami, consistent with RPLS. With conservative management, including tight blood pressure control, his symptoms improved and MRI findings resolved.
RPLS is a rare, but serious, clinicoradiologic syndrome which has been described as an adverse effect of many anti-angiogenic agents and should also be considered in patients on cediranib who present with neurologic symptoms along with vasogenic edema seen on MRI. If RPLS is suspected, cediranib should be discontinued and blood pressure should be aggressively controlled.
可逆性后部白质脑病综合征（RPLS）是一种罕见的临床影像学综合征，其特征为癫痫发作、头痛、视觉异常、意识模糊和脑病等神经症状，同时神经影像学检查显示后部白质存在血管源性水肿。已有报道称其与多种抗血管生成疗法相关，包括贝伐单抗、舒尼替尼、索拉非尼、帕唑帕尼和瑞戈非尼。西地尼布是一种强效的口服小分子酪氨酸激酶抑制剂，具有抗血管生成活性，已显示对多种实体瘤有活性。
我们报告一例65岁男性直肠转移性腺癌患者，其在一项I期临床试验中接受了西地尼布治疗。他出现了意识模糊和意识水平波动。脑部MRI显示大脑脚、脑桥和延髓弥漫性低水平T2信号异常，双侧丘脑有斑片状T2信号，符合RPLS表现。通过包括严格控制血压在内的保守治疗，他的症状得到改善，MRI表现也消失。
RPLS是一种罕见但严重的临床影像学综合征，已被描述为多种抗血管生成药物的不良反应，对于接受西地尼布治疗且出现神经症状以及MRI显示血管源性水肿的患者也应予以考虑。如果怀疑为RPLS，应停用西地尼布并积极控制血压。
