Petrányi Agota, Bodoky György
Fővárosi Önkormányzat Egyesített Szent István és Szent László Kórház, Onkológiai Osztály, Budapest.
Orv Hetil. 2011 Mar 6;152(10):379-91. doi: 10.1556/OH.2011.29060.
Neuroendocrine tumours are heterogeneous and rare malignancies arising from endocrine cells located in various anatomical locations. Neuroendocrine tumours can be functional and may produce a wide variety of mediators, however, the majority of neuroendocrine tumours do not produce biologically active hormones (non-functioning tumours). On the basis of their pathological and biological characteristics they can be well differentiated as low malignant and poorly differentiated highly malignant tumours. In the case of the advanced low malignant tumours the application of somatostatin analogues not only may control symptoms but they also have direct anti-tumour effect. The use of higher doses of somatostatin analogues or new subtype selective agonists, and chimeric or pan-somatostatin analogues will probably improve the clinical management of the patients who fail to respond to standard somatostatin analogue treatment. Data show that somatostatin analogues and interferon have a synergistic effect. The currently used chemotherapy in progressive neuroendocrine tumors is mainly devoted to poorly differentiated tumours, but also to well differentiated carcinomas which are either not eligible or resistant to other therapies. However, the new anti-tumoural agents, could eventually replace these old recipes in the near future. Clinical trials show that telozomide with capecitabine result in more favorable toxic profile and higher and longer response rate in the case of well-differentiated tumours. Targeted therapy became a new possibility in neuroendocrine tumours too. The monoclonal antibody bevacizumab, which affects the vascular endothelial growth factor receptors, has beneficial effects both in monotherapies and in combination with somatostatin analogues or with oxaliplatine and capecitabine. Recently, the low molecular multikinase inhibitor, sunitinib has demonstrated efficacy in pancreas neuroendocrine tumors, which was proven in a phase 3 trial. The mammalian target of the rapamycin inhibitor everolimus, currently investigated in phase 3 trials, was also efficient in the same subtype. Further trials are needed to determine that in the case of other types of neuroendocrine tumours which targeted therapy could be efficient. Radioisotope-labeled peptide receptor therapy with ¹³¹I-MIBG, ⁹⁰Y-DOTA-TOC or ¹⁷⁷Lu-DOTA-TOC may offer a highly effective option for patients with progressive and advanced stage of neuroendocrine tumours. The purpose of this review is to review and analyze data available regarding contemporary chemotherapeutic management of neuroendocrine tumours in order to determine which therapy should be applied in the therapeutic arsenal.
神经内分泌肿瘤是起源于位于不同解剖部位的内分泌细胞的异质性罕见恶性肿瘤。神经内分泌肿瘤可能具有功能性，可产生多种介质，然而，大多数神经内分泌肿瘤不产生生物活性激素（无功能性肿瘤）。根据其病理和生物学特征，它们可被很好地分为低恶性的高分化肿瘤和高恶性的低分化肿瘤。对于晚期低恶性肿瘤，应用生长抑素类似物不仅可以控制症状，还具有直接的抗肿瘤作用。使用更高剂量的生长抑素类似物或新的亚型选择性激动剂，以及嵌合或泛生长抑素类似物可能会改善对标准生长抑素类似物治疗无反应患者的临床管理。数据表明生长抑素类似物和干扰素具有协同作用。目前用于进展期神经内分泌肿瘤的化疗主要针对低分化肿瘤，但也适用于不符合其他治疗条件或对其他治疗耐药的高分化癌。然而，新的抗肿瘤药物最终可能在不久的将来取代这些旧方法。临床试验表明替莫唑胺联合卡培他滨在高分化肿瘤中产生更有利的毒性特征以及更高和更长的缓解率。靶向治疗在神经内分泌肿瘤中也成为一种新的可能。影响血管内皮生长因子受体的单克隆抗体贝伐单抗在单药治疗以及与生长抑素类似物或奥沙利铂和卡培他滨联合使用时均有有益效果。最近，低分子多激酶抑制剂舒尼替尼已在胰腺神经内分泌肿瘤中显示出疗效，这在一项3期试验中得到证实。目前正在3期试验中研究的雷帕霉素哺乳动物靶点抑制剂依维莫司在同一亚型中也有效。需要进一步的试验来确定靶向治疗在其他类型的神经内分泌肿瘤中是否有效。用¹³¹I - MIBG、⁹⁰Y - DOTA - TOC或¹⁷⁷Lu - DOTA - TOC进行放射性同位素标记的肽受体治疗可能为进展期和晚期神经内分泌肿瘤患者提供一种高效的选择。本综述的目的是回顾和分析有关神经内分泌肿瘤当代化疗管理的现有数据，以确定在治疗方案中应应用哪种治疗方法。
