Gastric neuroendocrine tumors: prevalence in Europe, USA, and Japan, and rationale for treatment with a gastrin/CCK₂ receptor antagonist

Abstract

Objective. Gastric carcinoids (neuroendocrine tumors) arise from enterochromaffin-like cells in the gastric mucosa. Most are caused by hypergastrinemia. The objectives were to determine if their prevalence in Europe, USA and Japan meets the criteria for an orphan disease and to justify treatment with a gastrin/CCK₂ receptor antagonist. Methods. We obtained data from European and USA cancer registries, and searched PubMed. Results. Prevalence per 10,000 population obtained from cancer registries was: median 0.32 (range 0.09–0.92) for Europe; and 0.17 for the USA, equivalent to 4812 for the whole population. A PubMed search for gastric carcinoids yielded prevalence for Japan only, which was 0.05 per 10,000 population, equivalent to 665 for the entire population. A further search for gastric carcinoids in patients with pernicious anemia (PA) or autoimmune chronic atrophic gastritis (CAG), two presentations of about 80% of gastric carcinoids, produced prevalence rates of 5.2–11%. Prevalence of PA itself was 0.12–1.9%. Data on CAG epidemiology were sparse. Conclusion. Prevalence of gastric carcinoids varied widely. All sources probably underestimate prevalence. However, prevalence was below the limits required for recognition by drug regulatory authorities as an orphan disease: 5 per 10,000 population of Europe; 200,000 for the whole population of the USA; and 50,000 for the whole population of Japan. Because gastric carcinoids are an orphan disease, and nonclinical and healthy volunteer studies support treatment with netazepide, a gastrin/CCK₂ antagonist, netazepide has been designated an orphan medicinal product in Europe and the USA for development as targeted treatment for gastric carcinoids.

Key Words:

• autoimmune chronic atrophic gastritis
• gastric carcinoids
• gastrin/CCK₂ receptor antagonist
• hypergastrinemia
• netazepide
• pernicious anemia

Acknowledgements

We thank: Alison Murray for helping to contact cancer registries; Libby Ellis and Professor Michel Coleman, Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, England, for obtaining information about gastric carcinoids from the National Cancer Registry for England; and Professor Nick Wald, Wolfson Institute of Preventative Medicine, London, England, for advice about estimating prevalence from incidence.

Declaration of interest: Netazepide (YF476) came from research by Ferring, Chilworth, England. Trio Medicines Ltd, England, a subsidiary of Hammersmith Medicines Research (HMR), has licensed netazepide from Ferring. Malcolm Boyce owns HMR, and Liv Thomsen is an employee of HMR.