, Volume 7, Issue 2, pp 117-125
Date: 02 Jun 2012

Sunitinib in pancreatic neuroendocrine tumors

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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 pancreatic neuroendocrine tumors. Sunitinib has demonstrated clinically 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 outcome 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 somatostatin analogues. Since the overall survival of patients with well-differentiated neuroendocrine tumors remains sufficiently 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.

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.