Systemic Sunitinib Malate Treatment for Advanced Juxtapapillary Retinal Hemangioblastomas Associated with von Hippel-Lindau Disease

Abstract

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.

Pazopanib in patients with von Hippel-Lindau disease: a single-arm, single-centre, phase 2 trial

“…Treatment with systemic bevacizumab provided marginal ocular benefit in individual case reports(12). Systemic treatment with sunitinib resulted in possible visual stabilization in three patients but with significant concomitant toxicity(13). Systemic therapy has been more broadly tested in patients with von Hippel-Lindau disease.…”

A retrospective case study of sunitinib treatment in three patients with Von Hippel-Lindau disease

“…For example, Kim et al, but not other studies, found that sunitinib may control the growth of lesions in the pancreas and cerebellum. Knickelbein et al found that treatment with sunitinib improved hemangioblastoma-related retinal edema in patients with VHL-related retinal hemangioblastomas, but did not improve their visual acuity or reduce the size of the tumor 16 . In contrast, Roma et al recorded radiological responses to sunitinib in renal, pancreatic, adrenal, hepatic, pulmonary, and subcutaneous tumors but not in hemangioblastomas 12 .…”

Pilot study of dovitinib in patients with von Hippel-Lindau disease

“…Surgical resection is currently the mainstay of managing these HBs if symptomatic or symptoms are impending. Systemic therapies such as sunitinib, a VEGF TKI, that are effective in VHL-associated RCC have not shown benefit for HBs [ 9 , 12 ]. Prospective biomarker studies of differentially expressed protein(s) in HBs versus RCCs versus other non-RCC lesions can greatly inform future trial design and treatment selection/sequence.…”