Pharmacologic therapy for neuroendocrine tumours]

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.