Öberg Kjell E
a Department of Endocrine Oncology, University Hospital, Uppsala University, Department of Medical Sciences, SE-751 85 Uppsala, Sweden.
Expert Rev Endocrinol Metab. 2011 Jan;6(1):49-62. doi: 10.1586/eem.10.81.
Neuroendocrine tumors (NETs) are a genetically diverse group of malignancies that sometimes produce peptides that cause characteristic hormonal syndromes. NETs can be clinically symptomatic (functioning) or silent (nonfunctioning); both types frequently synthesize more than one peptide, although often these are not associated with specific syndromes. Based on data from various sources, the incidence and prevalence of NETs is increasing. The primary treatment goal for patients with NETs is curative, with symptom control and the limitation of tumor progression as secondary goals. Surgery is the only possible curative approach and so represents the traditional first-line therapy. However, as most patients with NETs are diagnosed once metastases have occurred, curative surgery is generally not possible. Patients therefore require chronic postoperative medical management with the aim of relieving symptoms and, in recent years, suppressing tumor growth and spread. Somatostatin analogues, such as octreotide long-acting repeatable (LAR), can improve the symptoms of carcinoid syndrome and stabilize tumor growth in many patients. Results from the placebo-controlled, double-blind, prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors (PROMID study) demonstrate that octreotide LAR 30 mg is an effective antiproliferative treatment in patients with newly diagnosed, functionally active or inactive, well-differentiated metastatic midgut NETs. An antiproliferative effect can also be achieved with everolimus, and combination therapy with octreotide LAR has shown synergistic antiproliferative activity. Sunitinib, a tyrosine kinase inhibitor, is active in pancreatic NETs. In the future, pasireotide, the multireceptor targeted somatostatin analogue, has the potential to be an effective therapy for de novo or octreotide-refractory carcinoid syndrome and for inhibiting tumor cell proliferation. Peptide receptor radiotherapy with Yttrium-DOTATOC or Lutetium-DOTATE is also a new interesting treatment option for NETs.
神经内分泌肿瘤（NETs）是一组基因多样的恶性肿瘤，有时会产生导致特征性激素综合征的肽类物质。NETs在临床上可能有症状（功能性）或无症状（非功能性）；两种类型通常都会合成不止一种肽类物质，尽管这些肽类物质往往与特定综合征无关。根据来自各种来源的数据，NETs的发病率和患病率正在上升。NETs患者的主要治疗目标是治愈，其次是控制症状和限制肿瘤进展。手术是唯一可能的治愈方法，因此是传统的一线治疗方法。然而，由于大多数NETs患者在发生转移后才被诊断出来，通常无法进行根治性手术。因此，患者需要术后长期的药物治疗，目的是缓解症状，近年来还包括抑制肿瘤生长和扩散。生长抑素类似物，如长效可重复注射用奥曲肽（LAR），可改善类癌综合征的症状，并使许多患者的肿瘤生长稳定。关于长效可重复注射用奥曲肽对转移性神经内分泌中肠肿瘤患者肿瘤生长控制作用的安慰剂对照、双盲、前瞻性随机研究（PROMID研究）结果表明，30mg长效可重复注射用奥曲肽对新诊断的、功能活跃或不活跃的、高分化转移性中肠NETs患者是一种有效的抗增殖治疗。依维莫司也可实现抗增殖作用，与长效可重复注射用奥曲肽联合治疗已显示出协同抗增殖活性。舒尼替尼是一种酪氨酸激酶抑制剂，对胰腺NETs有效。未来，多受体靶向生长抑素类似物帕西瑞肽有可能成为治疗初发性或奥曲肽难治性类癌综合征以及抑制肿瘤细胞增殖的有效疗法。用钇-奥曲肽或镥-奥曲肽进行肽受体放射性治疗也是NETs一种新的有趣治疗选择。
