Netazepide, a gastrin/CCK2 receptor antagonist, can eradicate gastric neuroendocrine tumours in patients with autoimmune chronic atrophic gastritis.

Boyce, M, Moore, AR, Sagatun, L, Parsons, BN ORCID: 0000-0003-3599-1089, Varro, A, Campbell, F, Fossmark, R, Waldum, HL and Pritchard, DM ORCID: 0000-0001-7971-3561 (2017) Netazepide, a gastrin/CCK2 receptor antagonist, can eradicate gastric neuroendocrine tumours in patients with autoimmune chronic atrophic gastritis. British journal of clinical pharmacology.

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Gastric NETs type 1 manuscript. Revised 03Oct16 Clean with figures.docx - Author Accepted Manuscript
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Abstract

Netazepide, a gastrin/CCK2 receptor antagonist, once daily for 12 weeks reduced the number of tumours and size of the largest one in 16 patients with autoimmune chronic atrophic gastritis (CAG), achlorhydria, hypergastrinaemia and multiple gastric neuroendocrine tumours (type 1 gastric NETs), and normalised circulating chromogranin A (CgA) produced by enterochromaffin-like cells, the source of the tumours. The aim was to assess whether longer-term netazepide treatment can eradicate type 1 gastric NETs.After a mean 14 months off netazepide, 13 of the 16 patients took it for another 52 weeks. Assessments were: gastroscopy; gene-transcript expression in corpus biopsies using qPCR; blood CgA and gastrin concentrations; and safety assessments.While off-treatment, the number of tumours, the size of the largest one, and CgA all increased again. Netazepide for 52 weeks: cleared all tumours in 5 patients; cleared all but one tumour in one patient; reduced the number of tumours and size of the largest one in the other patients; normalised CgA in all patients; and reduced mRNA abundances of CgA and histidine decarboxylase in biopsies. Gastrin did not increase further, confirming that the patients had achlorhydria. Netazepide was safe and well tolerated.A gastrin/CCK2 receptor antagonist is a potential medical and targeted treatment for type 1 gastric NETs, and an alternative to regular gastroscopy or surgery. Treatment should be continuous because the tumours will regrow if it is stopped. Progress can be monitored by CgA in blood or biomarkers in mucosal biopsies. This article is protected by copyright. All rights reserved.

Item Type:	Article
Depositing User:	Symplectic Admin
Date Deposited:	07 Oct 2016 13:58
Last Modified:	19 Jan 2023 07:29
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3003667