Treatment of gastric carcinoids type 1 with the gastrin receptor antagonist netazepide (YF476) results in regression of tumours and normalisation of serum chromogranin A

Aliment Pharmacol Ther. 2012 Dec;36(11-12):1067-75. doi: 10.1111/apt.12090. Epub 2012 Oct 16.


Background: Patients with chronic atrophic gastritis have long-term gastric hypoacidity, and secondary hypergastrinaemia. Some also develop gastric ECL cells carcinoids (type 1 GC). Most type 1 GC remain indolent, but some metastasise. Patients undergo surveillance, and some are treated with somatostatin analogues, endoscopic resection or surgery. Netazepide (YF476) is a highly selective, potent and orally active gastrin receptor antagonist, which has anti-tumour activity in various rodent models of gastric neoplasia driven by hypergastrinaemia. Netazepide has been studied in healthy volunteers.

Aim: To assess the effect of netazepide on type 1 GC.

Methods: Eight patients with multiple type 1 GC received oral netazepide once daily for 12 weeks, with follow-up at 12 weeks in an open-label, pilot trial. Upper endoscopy was performed at 0, 6, 12 and 24 weeks, and carcinoids were counted and measured. Fasting serum gastrin and chromogranin A (CgA) and safety and tolerability were assessed at 0, 3, 6, 9, 12 and 24 weeks.

Results: Netazepide was well tolerated. All patients had a reduction in the number and size of their largest carcinoid. CgA was reduced to normal levels at 3 weeks and remained so until 12 weeks, but had returned to pre-treatment levels at 24 weeks. Gastrin remained unchanged throughout treatment.

Conclusions: The gastrin receptor antagonist netazepide is a promising new medical treatment for type 1 gastric carcinoids, which appear to be gastrin-dependent. Controlled studies and long-term treatment are justified to find out whether netazepide treatment can eradicate type 1 gastric carcinoids.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzodiazepinones / therapeutic use*
  • Carcinoid Tumor / blood
  • Carcinoid Tumor / drug therapy*
  • Chromogranin A / blood*
  • Female
  • Gastrins / blood
  • Humans
  • Male
  • Middle Aged
  • Phenylurea Compounds / therapeutic use*
  • Receptor, Cholecystokinin B / antagonists & inhibitors*
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / drug therapy*
  • Treatment Outcome


  • Benzodiazepinones
  • Chromogranin A
  • Gastrins
  • Phenylurea Compounds
  • Receptor, Cholecystokinin B
  • YF 476