苹果酸舒尼替尼全身治疗与冯·希佩尔-林道病相关的晚期视乳头旁视网膜血管母细胞瘤
Systemic Sunitinib Malate Treatment for Advanced Juxtapapillary Retinal Hemangioblastomas Associated with von Hippel-Lindau Disease.
作者信息
Knickelbein Jared E, Jacobs-El Naima, Wong Wai T, Wiley Henry E, Cukras Catherine A, Meyerle Catherine B, Chew Emily Y
机构信息
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD.
Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD.
出版信息
Ophthalmol Retina. 2017 May-Jun;1(3):181-187. doi: 10.1016/j.oret.2016.10.007.
PURPOSE
To describe the clinical course of advanced juxtapapillary retinal capillary hemangioblastomas (RCH) associated with von Hippel-Lindau (VHL) disease treated with systemic sunitinib malate, an agent that inhibits both anti-vascular endothelial growth factor and anti-platelet-derived growth factor signaling.
DESIGN
Observational case review.
PARTICIPANTS
Three patients with advanced VHL-related juxtapapillary RCH treated with systemic sunitinib malate.
METHODS
Patient 1 was followed routinely every 4 months while on systemic sunitinib prescribed by her oncologist for metastatic pancreatic neuroendocrine and kidney tumors. Patients 2 and 3 were part of a prospective clinical trial evaluating the use of systemic sunitinib for ocular VHL lesions during a period of 9 months. Visual acuity, size of RCH, and degree of exudation were recorded at each visit. Optical coherence tomography (OCT) and fluorescein angiography were also obtained at some visits.
MAIN OUTCOME MEASURES
Visual acuity, size of RCH, and degree of exudation.
RESULTS
Three patients with advanced VHL-associated juxtapapillary RCH were treated with systemic sunitinib malate. While none of the patients lost vision during therapy, treatment with sunitinib malate did not improve visual acuity or reduce the size of RCH. Improvements in RCH-associated retinal edema were observed in two patients. All patients experienced multiple adverse effects, including thyroid toxicity, thrombocytopenia, nausea, fatigue, jaundice, and muscle aches. Two of the three patients had to discontinue treatment prematurely and the third required dose reduction.
CONCLUSIONS
Systemic sunitinib malate may be useful in slowing progression of ocular disease from VHL-associated RCH. However, significant systemic adverse effects limited its use in this small series, and systemic sunitinib malate may not be safe for treatment of RCH when used at the doses described in this report. Further studies are required to determine if this medication used at lower doses with different treatment strategies, other medications in the same class or drugs directed at multiple targets in the tumor, may be safer and more effective for the treatment of advanced VHL-associated RCH.
目的
描述晚期视乳头旁视网膜毛细血管瘤（RCH）合并冯·希佩尔-林道（VHL）病患者接受全身应用苹果酸舒尼替尼治疗的临床过程。苹果酸舒尼替尼是一种同时抑制抗血管内皮生长因子和抗血小板衍生生长因子信号传导的药物。
设计
观察性病例回顾。
研究对象
3例晚期VHL相关视乳头旁RCH患者接受全身应用苹果酸舒尼替尼治疗。
方法
患者1在肿瘤内科医生为其转移性胰腺神经内分泌肿瘤和肾肿瘤开具的全身应用舒尼替尼治疗期间，每4个月常规随访一次。患者2和患者3是一项前瞻性临床试验的一部分，该试验在9个月期间评估全身应用舒尼替尼治疗眼部VHL病变的效果。每次就诊时记录视力、RCH大小和渗出程度。部分就诊时还进行了光学相干断层扫描（OCT）和荧光素血管造影检查。
主要观察指标
视力、RCH大小和渗出程度。
结果
3例晚期VHL相关视乳头旁RCH患者接受了全身应用苹果酸舒尼替尼治疗。虽然治疗期间无患者视力丧失，但苹果酸舒尼替尼治疗并未改善视力或减小RCH大小。2例患者的RCH相关视网膜水肿有所改善。所有患者均出现多种不良反应，包括甲状腺毒性、血小板减少、恶心、疲劳、黄疸和肌肉疼痛。3例患者中有2例不得不提前停药，第3例需要减量。
结论
全身应用苹果酸舒尼替尼可能有助于减缓VHL相关RCH所致眼部疾病的进展。然而，显著的全身不良反应限制了其在该小样本系列中的应用，且按照本报告所述剂量使用苹果酸舒尼替尼治疗RCH可能不安全。需要进一步研究以确定，使用更低剂量并采用不同治疗策略、同一类别的其他药物或针对肿瘤多个靶点的药物进行治疗，是否对晚期VHL相关RCH的治疗更安全、更有效。
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