Abstract
e22047 Background: Von Hippel Lindau (VHL) disease induces vascular lesions in multiple organs. Surgical intervention is the treatment of choice. Effective, safe systemic therapy will greatly improve the quality of life of these individuals. Methods: Patients with genetically confirmed VHL were enrolled on an IRB approved trial. Eligibility criteria included retinal angiomas, hemangioblastomas (HBs) measuring at least 5mm, renal cell carcinoma (RCC) 1 to 3 cm and pancreatic neuroendocrine tumors (NETs) 1 to 3 cm. Patients received sunitinib 50mg/day for 28 days/14 days off for four cycles. Scans were performed at baseline, and after cycles two and four. A separate set of 20 formalin-fixed paraffin embedded HBs and 20 RCCs were used for laser scanning cytometry (LSC) analysis of total and phospho vascular endothelial growth factor receptor (pVEGFR) and phospho platelet derived growth factor receptor (pPDGFR) levels in tumor endothelium. Results: Twelve patients were evaluable for response and toxicity. Eight had RCCs, nine had CNS lesions, and three had pancreatic NETs. Tumor size reduction was seen in 16/19 evaluable RCC lesions (95%CI 0.60, 0.97), 3/5 NETs (95%CI 0.15, 0.95) and 6/19 HBs (95%CI 0.13, 0.57). Two patients came off study for treatment related side effects, one patient progressed on study, and two patients did not complete the scheduled course of therapy. LSC analysis demonstrated significantly lower phospho VEGFR levels in HBs when compared with RCC. The mean (SD) of pVEGFR levels in log-transformation were 11.27 (0.49) and 11.75 (0.37) for HBs and RCC respectively (p = 0.003). The mean (SD) of pVEGFR to VEGFR ratio was .21 (0.12) versus 0.37 (0.43), for HBs and RCC respsectively (p = 0.043). Conclusions: Sunitinib treatment of patients with VHL resulted in consistent decrease of RCC and NET tumor size. The discrepant response to sunitinib in RCC and HBs may be explained by differential dependence on VEGFR activation in tumor endothelium. [Table: see text]
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