Department of Medicine, Johns Hopkins University/Sinai Hospital Program in Internal Medicine, Baltimore, MD, USA.
Dig Dis Sci. 2012 Jan;57(1):9-18. doi: 10.1007/s10620-011-1854-0. Epub 2011 Sep 22.
Neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas are slow-growing but commonly advanced malignancies with increasing incidence and prevalence. While locoregional disease can be effectively managed with resection, treatment of recurrent, progressive or metastatic disease has until recently been limited to palliative embolization and cytoreducitve surgery, with cytotoxic chemotherapeutic agents being the last resort. However, novel molecular targeted therapies inhibiting malignant cell proliferation and neoangiogenesis, as well as new cytotoxic chemotherapy drugs and somatostatin analogues, are all being investigated for their potential use in advanced neuroendocrine tumors. Long-acting release forms of octreotide have been shown to not only improve symptoms in carcinoid syndrome but to also delay progression of gastrointestinal NETs. On the other hand, phase III trials have demonstrated everolimus (with octreotide) and sunitinib to increase progression-free survival in pancreatic NETs. Use of bevacizumab has also shown promise in a phase II study, and results of an ongoing phase III trial comparing it to interferon are eagerly expected. Use of radiolabeled somatostatin analogues is still under investigation, though several phase II studies are encouraging. New cytotoxic agents, most notably temozolomide and capecitabine, are already in use, but their relative effectiveness compared to streptozocin in pancreatic NETs is yet to be determined.
胃肠道和胰腺的神经内分泌肿瘤（NET）生长缓慢，但通常是进展性的恶性肿瘤，发病率和患病率不断增加。虽然局部疾病可以通过手术切除有效地进行管理，但对于复发性、进行性或转移性疾病的治疗，直到最近还仅限于姑息性栓塞和细胞减灭术，细胞毒性化学疗法是最后的手段。然而，新型的分子靶向治疗药物，如抑制恶性细胞增殖和新生血管形成的药物，以及新型的细胞毒性化疗药物和生长抑素类似物，都在被研究用于治疗晚期神经内分泌肿瘤。长效奥曲肽释放剂型不仅可以改善类癌综合征的症状，还可以延缓胃肠道 NET 的进展。另一方面，III 期临床试验表明，依维莫司（联合奥曲肽）和舒尼替尼可延长胰腺 NET 的无进展生存期。贝伐单抗在一项 II 期研究中也显示出了希望，目前正在进行一项比较其与干扰素的 III 期临床试验，人们急切地期待着结果。放射性标记的生长抑素类似物的应用仍在研究中，尽管有几项 II 期研究令人鼓舞。新型细胞毒性药物，特别是替莫唑胺和卡培他滨，已经在使用，但它们在胰腺 NET 中的相对疗效与链脲佐菌素相比，还有待确定。
