REVIEW Sunitinib in pancreatic neuroendocrine tumors Eric Raymond & Pascal Hammel & Chantal Dreyer & Christian Maatescu & Olivia Hentic & Philippe Ruszniewski & Sandrine Faivre Received: 18 March 2012 / Accepted: 4 May 2012 / Published online: 2 June 2012 # Springer-Verlag 2012 Asbtract Sunitinib is an oral multitarget tyrosine kinase inhibitor with potent antiangiogenic properties. Preclinical data have demonstrated that pancreatic neuroendocrine tumors depend on vascular endothelial growth factor receptors and platelet growth factor receptors-signaling pathways for tumor angiogenesis. Sunitinib has recently been approved for the treatment of patients with advanced, progressive pancre- atic neuroendocrine tumors. Sunitinib has demonstrated clin- ically meaningful improvements in progression-free survival in a double-blinded randomized trial against placebo, setting progression-free survival as a valid endpoint for the evaluation of novel agents in patients with pancreatic neuroendocrine tumors. Although patients who progressed in this phase III trial were allowed to cross-over, a trend toward improvement in overall survival was also observed. In this trial, side effects reported with sunitinib were those previously reported in other tumor types, including hand–foot syndrome, diarrhea, and hypertension. This trial also investigated patient-reported out- come and showed that treatment with sunitinib did not affect quality of life of patient. Interestingly, this trial showed that sunitinib could be combined with somatostatin analogues without affecting the safety profile of either sunitinib or so- matostatin analogues. Since the overall survival of patients with well-differentiated neuroendocrine tumors remains suffi- ciently long, it is worth considering using alternate sequences of targeted therapy (such as everolimus) and chemotherapy to optimize the care of patients with advanced diseases. The optimal sequence for using chemotherapy, everolimus, and sunitinib will remain to be established in clinical trials. Keywords Angiogenesis . Pancreatic neuroendocrine tumor . PNET . Carcinoids . VEGFR . PDGFR . mTOR inhibitor . Endocrine tumors . Somatostatin analogues . Combinations Introduction Neuroendocrine tumors are malignancies arising from the endocrine cells of the digestive tract [1]. Survey data sug- gest that the incidence of well-differentiated neuroendocrine tumors is increasing worldwide and that the prevalence of the disease makes it one of the most frequent tumors of the gut [2]. For instance, the high prevalence of pancreatic Financial support This work was supported by the Foundation Nelia and Amadeo Barleta (FNAB) and by the Association d’Aide à la Recherche et à l’Enseignement en Cancérologie (AAREC). Other notes Information for this review was compiled by searching PubMed and MEDLINE databases for articles published until May 2011. Only articles published in English were considered. The search terms used included “pancreatic neuroendocrine tumor” in association with the search terms: “angiogenesis,”“VEGFR,”“PDGFR,” “sunitinib,”“everolimus,”“bevacizumab,”“mTOR inhibitors,” “rapamycin,”“rapalogues,”“temozolomide,”“streptozotocin,” “somatostatin analogs,”“IGF1-R inhibitor,”“natural product,” “metastatic,”“clinical trial,”“islet cell carcinomas,”“carcinoid tumors,”“targeted therapy,”“cytotoxic therapy,” and “prognosis.” Full articles were obtained, and references were checked for additional material and references when appropriate. Selected articles from a personal collection were also considered. E. Raymond (*) : C. Dreyer : C. Maatescu : S. Faivre Department of Medical Oncology (INSERM U728–Paris 7 Diderot University), Beaujon University Hospital, 100 boulevard du Général Leclerc, 92110 Clichy, France e-mail: eric.raymond@bjn.aphp.fr P. Hammel : O. Hentic : P. Ruszniewski Department of Gastro-entero-pancreatology, Beaujon University Hospital, 100 boulevard du Général Leclerc, 92110 Clichy, France Targ Oncol (2012) 7:117–125 DOI 10.1007/s11523-012-0220-2