BACKGROUND: Neuroendocrine tumors (NETs) are neoplasms arising most often in the GI tract, pancreas, or lung. Diagnosis of NETs is often delayed until the disease is advanced, because of the variable and nonspecific nature of the initial symptoms. Surgical resection for cure is therefore not an option for most patients. METHODS: Somatostatin analogues represent the cornerstone of therapy for patients with NETs. This article reviews the important role that somatostatin analogues continue to play in the treatment of patients with NETs. RESULTS: Octreotide was the first somatostatin analogue to be developed; more than 30 years of data have accumulated demonstrating its efficacy and safety. Lanreotide is another somatostatin analogue in clinical use, and pasireotide is a promising somatostatin analogue in development. Newer long-acting depot formulations are now available offering once-monthly administration. Although octreotide was initially developed for symptom control, recent results indicate that it also has an antiproliferative effect, significantly increasing time to progression in patients with midgut NETs. Combinations of octreotide with other targeted therapies may further improve patient outcomes. Findings in recent studies of the combination of octreotide and the mTOR inhibitor everolimus are encouraging. The combinations of octreotide with other agents (eg, interferon-α, bevacizumab, cetuximab, AMG-706, and sunitinib) are being investigated. CONCLUSIONS: Somatostatin analogues have been used to treat the symptoms of NETs for decades and also have an antineoplastic effect, markedly prolonging progression-free survival. Somatostatin analogues are likely to remain the cornerstone of treatment for most patients with advanced NETs. Promising new combination therapies are undergoing clinical investigation. Neuroendocrine tumors (NETs) are epithelial neoplasms that undergo predominantly neuroendocrine differentiation and arise in many organs of the body. 1 Although NETs are uncommon, the reported incidence has been steadily increasing. An analysis of 35,825 NET cases in the Surveillance, Epidemiology, and End Results database demonstrated a 5-fold increase in the annual age-adjusted incidence of NETs from 1.09/100,000 population in 1973 to 5.25/100,000 population in 2004. 2 NETs are often classified by their organ of origin (eg, lung, pancreas, or gastrointestinal tract) and by their secretion of various peptides and neuroamines. 3 Functional NETs are defined by the presence of a clinical syndrome caused by excessive hormone secretion. An example is carcinoid syndrome from the secretion of serotonin and other vasoactive substances, resulting in diarrhea and flushing. 4 In contrast, nonfunctional NETs have no specific clinical syndrome but may still secrete peptides or neuroamines, measurable in plasma or urine. NETs are classified as either well differentiated (low and intermediate grade) or poorly differentiated (high grade). NET survival rates vary by primary site and grade and are lower in patients with poorly differentiated tumors than in those with well-differentiated tumors and in distant vs. locoregional disease. 2 This review is focused on the treatment of patients with well-differentiated NETs. If NETs are diagnosed early, surgical resection is often curative. 5 – 7 However, the variable and nonspecific symptoms of NETs often delay diagnosis until the disease has progressed to an advanced state, when complete surgical resection may no longer be possible. More than 50% of NETs are unresectable at diagnosis. 8 Metastatic NETs can be treated with localized therapy for liver metastases (eg, resection, radiofrequency ablation, hepatic artery radioembolization, chemoembolization, and bland embolization) and systemic management with chemotherapy and biologic therapies (eg, interferon [IFN]-α, antiangiogenic drugs, mammalian target of rapamycin [mTOR] inhibitors, multikinase inhibitors, and peptide receptor radiotherapy). 4 , 9 – 11 Somatostatin analogues (SSAs) play a central role in managing the symptoms of excessive hormone secretion and appear to control tumor growth. 12 – 15
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