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.
Ther Adv Med Oncol. 2012 Jan;4(1):9-18. doi: 10.1177/1758834011428147.
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.
基于 RIP1-Tag2 转基因小鼠模型中的临床前数据，舒尼替尼是一种血管生成抑制剂，可分别阻断血管内皮生长因子受体和血小板衍生生长因子受体在内皮细胞和周细胞中的作用。I 期临床试验中客观缓解的证据证明，舒尼替尼在晚期/转移性高分化胰腺神经内分泌肿瘤患者中的大型 II/III 期方案是合理的。在 II 期研究中，舒尼替尼显示出强大的抗肿瘤活性和安全的毒性特征。在最近的一项双盲安慰剂对照随机 III 期试验中，舒尼替尼使患者的无进展生存期增加了一倍，诱导了客观缓解，并降低了晚期/转移性高分化肿瘤患者的死亡风险。这些数据使得舒尼替尼在包括欧洲和美国在内的多个国家获得批准。这些最新数据为高分化胰腺神经内分泌肿瘤患者带来了希望，并将改变这种疾病的治疗标准。
