Sunitinib in advanced pancreatic neuroendocrine tumors: latest evidence and clinical potential.
Based on preclinical data available in the RIP1-Tag2 transgenic mouse model, sunitinib is an inhibitor of angiogenesis in pancreatic neuroendocrine tumors blocking vascular endothelial growth factor receptors and platelet-derived growth factor receptors in endothelial cells and pericytes, respectively. Evidence of objective response in phase I trials justified the initiation of a large phase II/III program using sunitinib in patients with advanced/metastatic well-differentiated pancreatic neuroendocrine tumors. In the phase II study, sunitinib showed potent antitumor activity and a safe toxicity profile. In a recent double-blind placebo-controlled randomized phase III trial, sunitinib doubled the progression-free survival of patients, induced objective responses, and reduced the risk of death of patients with advanced/metastatic well-differentiated tumors. These data allowed the approval of sunitinib in several countries including Europe and the United States of America. These recent data provide hope for patients with well-differentiated pancreatic neuroendocrine tumors and will change standards of care in this disease.
Department of Medical Oncology, Univ Paris Diderot, Sorbonne Paris Cité, INSERM U728, and Beaujon and Louis Mourier University Hospital (Assistance Publique Hopitaux de Paris, Paris 7 Diderot), Clichy, France.
Catherine
C
Delbaldo
Sandrine
S
Faivre
Chantal
C
Dreyer
Eric
E
Raymond