Abstract
Purpose: :
Optic nerve hemangioblastomas (ONH) of von Hippel-Lindau (VHL) disease respond poorly to current treatments. Sunitinib malate, which targets the cell surface receptors of platelet derived growth factor (PDGF) in addition to vascular endothelial growth factor (VEGF), may be a potential therapy for the mature vasculature of ONH. Our case series explores the safety of oral sunitinib malate in the treatment of ONH.
Methods: :
Three females (aged 32, 45, 52 years) with genetically confirmed VHL and ONH were evaluated while taking sunitinib malate. Patients 1 and 2 were in a pilot study with ophthalmic exams every 2 weeks; patient 3 was part of a natural history study, taking sunitinib malate for a neuroendocrine tumor and undergoing an ophthalmic exam every 3 months. Each patient received sunitinib malate orally, once daily in cycles of 4 weeks followed by a 2 week rest period according to the standard chemotherapy regimen. Fundus photographs, adverse events and optical coherence tomography were reviewed.
Results: :
All patients experienced multiple side effects. Drug holidays beyond the standard 2 week rest period occurred for safety concerns. Patient 1 took sunitinib malate 50mg over a study period of 19 weeks with a drug holiday; she withdrew after developing thyroiditis. Patient 2 initially took sunitinib malate 50mg which was decreased to 37.5mg during the second cycle over a study period of 25 weeks with several drug holidays; she withdrew after developing neutropenia and thrombocytopenia. Patient 3 has been taking sunitinib malate for 5 years, initially at 50mg which was reduced to 25mg after the first cycle; she initially had intolerable constitutional symptoms which improved with dose reduction. At the end of the pilot study, patient 1’s tumor had moderate lipid regression and decreased vascularity. Patient 2 remained stable. Patient 3 showed a decrease in tumor size and fibrosis. Visual acuity remained stable in all patients, ranging from light perception to 20/125.
Conclusions: :
In this interventional case series of ONH, the systemic side-effects of sunitinib malate were tolerated in only one patient on a reduced dose. However, the potential to decrease ONH tumor size and exudation warrants further investigation. A local injection of a combination of anti-PDGF and anti-VEGF agents may be preferable to limit systemic effects.
Clinical Trial: :
http://www.clinicaltrials.gov NCT00673816
Keywords: retina • drug toxicity/drug effects • tumors