Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies

ABSTRACT

Introduction: Neuroendocrine tumors(NETs), once thought rare, are increasing in frequency in most countries and receiving increasing-attention. NETs present two-treatment problems. A proportion is aggressive and a proportion has a functional, hormone-excess-state(F-NET), each of which must be treated. Recently, there have been many advances, well-covered in reviews/consensus papers on imaging-NETs; new, novel anti-tumor treatments and understanding their pathogenesis. However, little attention has been paid to advances in the treatment of the hormone-excess-state. These advances are usually reported in case-series, and case-reports with few large studies. In this paper these advances are reviewed.

Areas covered: Advances in the last 5-years are concentrated on, but a review of literature from the last 10-years was performed. PubMed and other databases (Cochrane, etc.) were searched for F-NET-syndromes including carcinoid-syndrome, as well as meeting-abstracts on NETs. All advances that controlled hormone-excess-states or facilitated-control were covered. These include new medical-therapies [serotonin-synthesis inhibitors(telotristat), Pasireotide, new agents for treating ACTHomas], increased dosing with conventional therapies (octreotide-LAR, Lanreotide-Autogel), mTor inhibitors(everolimus), Tyrosine-kinase inhibitors(sunitinib),cytoreductive surgery, liver-directed therapies (embolization, chemoembolization, radioembolization, RFA), peptide radio-receptor-therapy(PRRT) and ¹³¹I-MIBG, ablation of primary F-NETs.

Expert opinion: Although many of the newer therapies controlling the hormone-excess-states in F-NETs are reported in relatively few patients, all the approaches show promise. Their description also generates some controversies/unresolved areas,such as the order of these new treatments, their longterm-efficacy, and effectiveness of combinations which may require large,controlled studies.

KEYWORDS:

• Acid hypersecretion
• carcinoid syndrome
• chemoembolization
• chemotherapy
• cytoreductive surgery
• embolization
• gastrinoma
• insulinoma
• Lanreotide
• multiple endocrine Neoplasia type 1
• neuroendocrine tumor
• pancreatic endocrine tumor
• peptide radio-receptor therapy
• octreotide
• radioembolization
• radio-frequency ablation
• SIRT
• somatostatin analogues
• telotristat
• Zollinger-Ellison syndrome

Article highlights

• Patients with functional neuroendocrine tumors(F-NETs) have two treatment problems: treatment of the hormone-excess state and directed at tumor growth/malignancy

• Recently there are many advances in antitumor therapies, which are well covered in reviews, but little analysis of advances in treatments of hormone-excess states

• In contrast to antitumor studies, most advances in treatment of hormone-excess states are in small series, case series, case reports.

• Numerous new treatments of the hormone-excess states are reported including: medical therapies [mTor-inhibitors (everolimus), tyrosine-kinase inhibitors (sunitinib), increases dosages of conventional agents (somatostatin-analogs)]; peptide-radioreceptor therapy and increased use of ¹³¹I-MIBG; cytoreductive surgery; ablation of F-NET primaries; liver-directed therapies (embolization, chemoembolization, radioembolization, RFA); therapies directed at specific syndromes [serotonin-synthesis inhibitors(telotristat),pasireotide, new agents for Cushing’s syndrome with ACTHomas]

• The evidence for the use of each approach is reviewed and the unresolved areas and controversies discussed

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

Partial funding for this study was provided by Intramural Digestive Diseases Branch, NIDDK, NIH (Z-021).