Management of Neuroendocrine Tumors: Current and Future Therapies

Kjell E Öberg


Expert Rev Endocrinol Metab. 2011;6(1):49-62. 

In This Article

Abstract and Introduction


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 90Yttrium-DOTATOC or 177Lutetium-DOTATE is also a new interesting treatment option for NETs.


Neuroendocrine tumors (NETs) are a genetically diverse spectrum of malignant solid tumors arising from the secretory cells of the neuroendocrine system that produce peptides causing characteristic hormonal syndromes. NETs can be clinically symptomatic (i.e., 'functioning'), or silent, (i.e., 'nonfunctioning'). Survey data from the Surveillance, Epidemiology, and End Results (SEER) program demonstrated that the incidence of malignant NETs is increasing,[1] although this may partly be due to increased physician awareness and improved diagnostic techniques. Nevertheless, in 2004 there were 5.25 new cases of NETs per 100,000 people, compared with 1.09 per 100,000 in 1973 (age-adjusted incidence).[1] This is in contrast to the overall incidence of malignancies, which has remained relatively consistent since 1992. Data from the Norwegian Registry of Cancer showed a similar incidence of NETs; there was a 72% increase between 2000 and 2004 compared with 1993–1997.[2] Ethnic differences in the risk of developing a NET are also apparent, with a higher incidence in African–American than Caucasian patients.[2–4] The potential genetic factors are currently unknown. The most frequently diagnosed NETs in the USA are small intestine tumors, lung and rectum, and these have seen the greatest increase in incidence since 1974. A time-trend analysis demonstrated a statistically significant increase in incidence across all disease stages at diagnosis (p < 0.001; Figure 1).[1]

Figure 1.

Incidence of malignant neuroendocrine tumors between 1973 and 2003 by disease stage.
Adapted with permission from [1].


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