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

Abstract

Von Hippel-Landau (VHL) disease is characterized by malignant and benign tumors in multiple organs. Sunitinib, a tyrosine kinase inhibitor, has been clinically available for treating sporadic patients with recurrent or unresectable and metastatic clear renal cell carcinomas (cRCCs) and metastatic lesions of the lung, but its effect on VHL disease-associated tumors remains poorly understood. This retrospective case series examined the effect of sunitinib on RCC, hemangioblastomas, pheochromocytomas, and pancreatic neuroendocrine tumors in patients with confirmed VHL. Of note, three patients with VHL disease who were treated with sunitinib were identified from a review of their medical records. The efficacy of sunitinib was evaluated by comparing computed tomography (CT) or magnetic resonance imaging (MRI) scans conducted before and after treatment. Adverse side effects associated with sunitinib were assessed and recorded. All three patients with VHL disease exhibited clinical improvement after treatment with sunitinib. Patient 1 exhibited a decrease in the size of both their pheochromocytoma and RCC after 19 months of sunitinib treatment. RCCs in Patients 2 and 3 exhibited stable response to sunitinib for approximately 1 and 6 years, respectively. All the patients reported tolerable side effects. Therefore sunitinib treatment was associated with either partial response or stable control of VHL-related RCCs, pheochromocytomas and pancreatic neuroendocrine tumor (NET) with acceptable side effects. Further evaluation of sunitinib in patients with VHL disease in larger prospective studies is warranted.

The Efficacy and Safety of Tyrosine Kinase Inhibitors for Von Hippel–Lindau Disease: A Retrospective Study of 32 Patients

“…In 12 patients receiving TKI therapy for more than 3 years, we observed that pancreatic lesions and renal cysts were not cancerous and generally did not require treatment. Of the five CHBs, one achieved a partial response after 2 months of axitinib therapy, and of the six pheochromocytomas, 1 (17%) achieved a partial response after 6 months of axitinib therapy, which has rarely been reported in previous studies (21, 27).…”

“…Currently, small-molecule tyrosine kinase inhibitors (TKIs), including sunitinib, sorafenib, axitinib, and pazopanib, mainly target the VEGF pathway by inhibiting VEGF ligands or its receptors (14–16). Several studies have reported clinical outcomes in patients with VHL disease treated with TKIs (17–21). A pilot trial by Jonasch et al (17) assessed the activity and safety of sunitinib in 15 patients with VHL disease, and their results revealed that 6 of the 18 RCCs (vs. none of the CHBs) exhibited a partial response, while the sunitinib dose had to be reduced in 10 patients (17).…”

The VHL/HIF Axis in the Development and Treatment of Pheochromocytoma/Paraganglioma

“…Several clinical trials have suggested that patients with metastatic PPGLs responded well to sunitinib (136)(137)(138)(139)(140). Results from one of our recent studies also suggested that sunitinib could be an optional therapy for patients with VHL disease-associated PCCs (141). Results from the SNIPP trial showed that sunitinib at 50mg daily benefited most patients with progressive PPGLs.…”

Pancreatic neuroendocrine tumours in patients with von Hippel-Lindau disease

“…In advanced disease, as in sporadic PNETs, treatment includes peptide receptor radioligand therapy (PRRT), chemotherapy, and molecularly targeted therapy [24]. In patients with VHL, who are affected at the same time by PNET and other VHL-related tumours, (pheochromocytoma, RCC, haemangioblastoma) sunitinib therapy led to mass reduction in all tumor types [36].…”