胰腺神经内分泌肿瘤的药物治疗及其进展

Medical treatment and its advances of pancreatic neuroendocrine neoplasms

胰腺神经内分泌肿瘤(pNENs)的发病率在不断升高。20%~64%的pNENs在确诊时已发生远处转移,而功能性肿瘤在p NENs中相对多见。因此,药物治疗在p NENs中具有非常重要的地位。生长抑素类似物(SSAs)是p NENs的主要治疗药物之一,新一代的SSAs尚不足以取代兰瑞肽水凝胶或长效奥曲肽用于治疗增殖指数较低且生长抑素受体表达阳性的胰腺神经内分泌瘤(p NET);依维莫司和舒尼替尼是目前被推荐用于p NET的两种靶向药物,其他靶向药物在p NET中也已逐渐开展临床试验,部分药物已进入Ⅲ期临床试验;化疗主要用于生长速度较快的p NET及分化差的神经内分泌癌(NEC),新方案临床试验多针对NEC;肽受体放射性核素治疗(PRRT)在生长抑素受体表达阳性的p NET中可能具有重要治疗价值;p NENs的免疫治疗临床试验的初步结果并未显示出非常好的疗效;联合不同药物或方案治疗p NENs尚处于早期探索阶段。总之,p NENs药物治疗虽已取得较大的进展,但很多治疗药物尚处于试验阶段,距离临床应用尚远。

The incidence rate of pancreatic neuroendocrine neoplasms(pNENs)is continuously increasing.Since 20%to64%of pNENs develops metastatic disease when diagnosed and functional pNENs is quite common,medical treatment is of great importance for pNENs.Somatostatin analogues(SSAs)is one of the major medical treatments for pNENs and the new generation of SSAs cannot replace the role of lanreotide autogel and octreotide long-acting repeatable(LAR)for pancreatic neuroendocrine tumor(pNET)with low proliferative index and positive expression of somatostatin receptors(SSTRs).Everolimus and sunitinib are two targeted treatments recommended for pNET.Clinical trials of other targeted treatments are gradually conducted with some of them already reached phaseⅢ.Chemotherapy is usually applied in pNENs with high growth rate or poorly-differentiated neuroendocrine carcinoma(NEC).Most clinical trials of new chemotherapy scheme are designed for NEC.Peptide receptor radionuclide therapy(PRRT)may have important value in pNET positively expressing SSTRs.Preliminary data of immunotherapy for pNENs did not show very promising result and studies of different medical treatments combinations for pNENs are still under exploration.In general,although medical treatments for pNENs had achieved great advances,there is still a long way to go before many new treatments can be used in pNENs.