Sunitinib Efficacy in Advanced Pancreatic Neuroendocrine Tumors

Abstract

Pancreatic neuroendocrine tumors (PNETs) are relatively rare and generally considered to follow an indolent course. However poorly differentiated or metastatic PNETs can also behave in an aggressive manner with a 5-year survival as low as 30% in non-functioning PNETs. Many therapeutic agents have been tested in the treatment of NET including Interferon alfa, streptozocin or temozolomide-based combination chemotherapy with an objective response of 10%–30%. Moreover these agents are less effective in patients with advanced carcinoid tumors and their prolonged use is often associated with added toxicity. A number of other signaling pathways have also been implicated in neuroendocrine tumors, which also express platelet-derived growth factor (PDGF), PDGF receptor (PDGFR), insulin-like growth factor-1, insulin-like growth factor receptor, basic fibroblast growth factor, transforming growth factor, epidermal growth factor receptor, and stem-cell factor receptor. Sunitinib malate (SUTENT®; Pfizer Oncology) is a small molecule kinase inhibitor with activity against a number of tyrosine kinase receptors, including VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-, PDGFR-, stem-cell factor receptor, glial cell line derived neurotrophic factor receptor and FMS-like tyrosine kinase-3. This review will present data regarding sunitinib progress in PNET, demonstrating its effectiveness and the emerging hope it may provide for such a disease with limited treatment options.