First-Line sunitinib in patients with renal cell carcinoma (RCC) in von Hippel–Lindau (VHL) disease: clinical outcome and patterns of radiological response

Abstract

rate of radiological response, patterns of responses in different organs, treatment-related toxicities. We performed a retrospective analysis of sunitinib therapy in genetically-confirmed VHL patients treated at our Institution for multifocal or advanced RCC. From February 2007 to July 2012, 14 VHL patients started first-line sunitinib for recurrent or progressing RCC, mean age 48 years (27-71). Nine patients achieved a partial RECIST response (64.3%); responses were noted not only in renal and hepatic lesions but also in pancreatic nodules. Most lesions showed density reduction, while all CNS haemangioblastoma lesions remained stable. At a median follow-up of 37 months, six patients have progressed and three patients died, with a progression-free rate at 2 years of 71.4%. Sunitinib may therefore achieve a fairly good disease control in VHL patients. Radiological responses may be obtained not only in renal tumors but also in synchronous VHL-related lesions, especially pancreatic solid nodules whose exact nature (metastatic RCC or neuroendocrine tumor) cannot be ruled out without invasive biopsy.

Attainment of a Long-term Favorable Outcome by Sunitinib Treatment for Pancreatic Neuroendocrine Tumor and Renal Cell Carcinoma Associated with von Hippel-Lindau Disease

“…Moreover, another international phase III trial for sporadic pancreatic neuroendocrine tumors demonstrated a relatively lower efficacy of sunitinib, PR of 9% and PFS of 11 months (10), whereas a phase II trial for sporadic pancreatic neuroendocrine tumors conducted in Japan reported a relatively favorable efficacy of sunitinib, PR of 50%, despite the small number of patients available for the analysis (n = 12) (22). The favorable outcome of our patient with PR maintenance from sunitinib therapy for nearly 5 years against RCC and pancreatic neuroendocrine tumor is in agreement with the results from these earlier reports (18)(19)(20)22) and suggests that sunitinib treatment is also effective in Japanese populations with VHL disease. Further prospective studies are required to elucidate whether patients with VHL disease have a better outcome from sunitinib treatment than patients with sporadic RCC or pancreatic neuroendocrine tumors.…”

“…Kim et al reported that all four patients with VHL disease-associated metastatic RCC treated with sunitinib exhibited PR with a treatment duration of 19-51 months (19). More recently, Roma et al have shown in their retrospective analysis that 9 of 14 (64%) patients with recurrent or advanced RCC who received sunitinib treatment as a first-line therapy achieved PR, with a 2-year PFS of 71% (20). These studies, despite a relatively small number of patients analyzed, suggest that sunitinib treatment is even more effective in patients with VHL disease compared to those with sporadic RCC or pancreatic neuroendocrine tumor.…”

Sunitinib for the treatment of benign and malignant neoplasms from von Hippel-Lindau disease: A single-arm, prospective phase II clinical study from the PREDIR group

“…good for renal tumor lesions and little or no activity against hemangioblastomas) [13]. This pattern was also seen in a case report and a retrospective case review of VHL disease patients who had responses in mRCC tumors, but not other VHL lesions, after sunitinib [11, 14]. In addition, prolonged partial responses to sunitinib were reported for mRCC lesions in a series of four VHL disease cases [15].…”

Pharmacological HIF2α inhibition improves VHL disease–associated phenotypes in zebrafish model

“…Therefore, it is conceivable that HIF2α inhiinhibitors has a modest, at best, effect on RCC lesions only. Published reports indicated a partial response of metastatic or locally advanced RCC in patients with VHL (36)(37)(38)(39). No medical therapy for HB exists so far; there has been no evidence of HB response to VEGF inhibitors in the patients with VHL treated for RCC.…”