1,721,037 research outputs found
The expanding role of somatostatin analogs in gastroenteropancreatic and lung neuroendocrine tumors
No full textSomatostatin analogs (SSAs) were initially developed as antisecretory agents used for the control of hormonal syndromes associated with neuroendocrine tumors (NETs). In recent years, accumulating evidence has also supported their role as antiproliferative agents in well or moderately differentiated NETs. The phase III PROMID trial demonstrated that octreotide long-acting repeatable (LAR) can significantly prolong time to progression among patients with metastatic midgut NETs. More recently, the randomized CLARINET trial reported a significant improvement in progression-free survival in a heterogeneous population of patients with gastroenteropancreatic (GEP)-NETs treated with depot lanreotide. Octreotide and lanreotide target somatostatin receptor subtypes in a similar fashion, and appear to be clinically interchangeable; however, comparative noninferiority trials have not been performed. Further studies are needed to evaluate the efficacy of novel SSAs such as pasireotide in the refractory setting, and the role of high-dose SSAs for symptom and tumor control
An update on gastroenteropancreatic neuroendocrine tumors
No full textGastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of neoplasms arising from the diffuse neuroendocrine system. The incidence of GEP-NETs has increased markedly over the past 3 decades, probably as a result of trends in imaging and improvements in diagnosis. Advances in molecular biology have translated into an expansion of treatment options for patients with GEP-NETs. Somatostatin analogs, initially developed for control of hormonal syndromes, have recently been proven to inhibit tumor growth. Newer drugs, targeting angiogenesis and mammalian target of rapamycin (mTOR) pathways, have been approved for progressive pancreatic NETs; however, their role in nonpancreatic NETs remains controversial. Alkylating cytotoxic agents, such as streptozocin and temozolomide, play an important role in the treatment of pancreatic NETs, although estimated response rates vary widely and phase III data are lacking. During the next few years, randomized clinical trials are expected to provide more clarity regarding the role of radiolabeled somatostatin analogs. Predictive biomarkers that would allow for individualized selection of treatments are needed
Is NETTER-2 a practice-changing trial?
No full textThe NETTER-2 trial provides the first phase III evidence that 177Lu-dotatate is active as first-line therapy in patients with gastroenteropancreatic neuroendocrine tumours with a Ki-67 proliferative index of 10–55%. This approach is an important addition to the first-line therapeutic armamentarium, although treatment selection based on patient-specific and tumour-specific characteristics remains appropriate
Radionuclide Therapy for Neuroendocrine Tumors
No full textPeptide receptor radionuclide therapy (PRRT) is a form of systemic radiotherapy that allows targeted delivery of radionuclides to tumor cells expressing high levels of somatostatin receptors. The two radiopeptides most commonly used for PRRT, 90Y-DOTATOC and 177Lu-DOTATATE, have been successfully employed for more than a decade for the treatment of advanced neuroendocrine tumors (NETs). Recently, the phase III, randomized NETTER-1 trial has compared 177Lu-DOTATATE versus high-dose octreotide LAR in patients with progressive, metastatic midgut NETs, demonstrating exceptional tolerability and efficacy. This review summarizes recent developments in the field of radionuclide therapy for gastroenteropancreatic and lung NETs and considers possible strategies to further enhance its clinical efficacy
Peptide receptor radionuclide therapy in G3 gastroenteropancreatic neuroendocrine tumors: a missed opportunity for European patients?
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Gastroenteropancreatic Neuroendocrine Tumors
Get PDFNeuroendocrine tumors (NETs) are heterogeneous malignancies arising from the diffuse neuroendocrine system. They frequently originate in the gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their incidence has steadily increased in the last 3 decades. Fundamental biologic and genomic differences underlie the clinical heterogeneity of NETs, and distinct molecular features characterize NETs of different grades and different primary sites. Although surgery remains the cornerstone of treatment for localized tumors, systemic treatment options for patients with metastatic NETs have expanded considerably. Somatostatin analogs have demonstrated both antisecretory and antitumor efficacy. Peptide receptor radionuclide therapy with lutetium-177 dotatate (177 Lu-DOTATATE) has been approved for advanced GEP-NETs. The antitumor activity of everolimus has been demonstrated across a wide spectrum of NETs, and the antiangiogenic agent sunitinib has been approved for pancreatic NETs (pNETs). Chemotherapy with temozolomide and capecitabine has recently demonstrated an unprecedented prolongation of progression-free survival in a randomized trial of pNETs. Multiple retrospective series have reported the efficacy of liver-directed therapies both for palliating symptoms of hormone excess and for controlling tumor growth. Telotristat, an oral inhibitor of tryptophan hydroxylase, has been shown to reduce diarrhea in patients with carcinoid syndrome. Defining the therapeutic algorithm and identifying biomarkers predictive of response to treatments are among the main priorities for the next decade of research in the NET field
Will clinical heterogeneity of neuroendocrine tumors impact their management in the future? Lessons from recent trials
No full textPurpose of review Neuroendocrine tumors (NETs) are a group of biologically and clinically heterogeneous neoplasms arising from the diffuse neuroendocrine system. In the last few years, advances in our understanding of the biology of these tumors have translated into an expansion of treatment options for patients with NETs. Current treatment modalities include somatostatin analogs (SSAs), radiolabeled SSAs, targeted agents, cytotoxic drugs and liver-directed therapies for the management of metastatic disease. Recent findings Recent studies have expanded the role of SSAs in gastroenteropancreatic (GEP)-NETs, and everolimus has shown robust antitumor activity across a broad range of NETs of the lung and GEP tract. The radiolobeled SSA 177 Lu-DOTATATE has been investigated in a randomized phase III trial, and has demonstrated exceptional efficacy and tolerability in patients with progressive midgut NETs. The new serotonin inhibitor telotristat etiprate has shown significant activity in the palliation of symptoms of carcinoid syndrome, and its approval by regulatory authorities is expected soon. Summary The field of NETs has been transformed from one dominated by limited treatment options to one characterized by an increasing number of therapeutic agents and active clinical trials. Navigating the current therapeutic algorithm may be challenging, and requires an understanding both of the heterogeneity of NETs and of characteristics that are shared by NETs across tumor subtypes
Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors
Get PDFTreatment options for neuroendocrine tumors (NETs) and carcinomas (NECs) are expanding. Early-phase studies have shown preliminary evidence of the antitumor activity of alpha-emitting peptide receptor radionuclide therapy (PRRT), and novel radiopeptides incorporating somatostatin receptor antagonists (rather than agonists) have been developed. Several tyrosine kinase inhibitors (TKIs) with antiangiogenic potential have been evaluated in patients with NETs, including lenvatinib, axitinib, cabozantinib and pazopanib. Recently, two phase 3 clinical trials have demonstrated the efficacy and safety of surufatinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, -3, fibroblast growth factor receptor (FGFR)-1 and colony stimulating factor-1 receptor (CSF-1R), in patients with pancreatic and extra-pancreatic NETs. Multiple clinical trials of combination immunotherapy have been recently completed, but interpretation of the results is hampered by small samples sizes and discordant outcomes. This review summarizes recent data on emerging treatments for neuroendocrine neoplasms
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