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

Abstract

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.

• Authors: R Fossmark, Ø Sørdal, C S Jianu, G Qvigstad, I S Nordrum, M Boyce, H L Waldum
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 36 Issue 11-12 Pg. 1067-75 (Dec 2012) ISSN: 1365-2036 [Electronic] England
• PMID: 23072686 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

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

Topics

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