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Treatment of gastric carcinoids type 1 with the gastrin receptor antagonist netazepide (YF476) results in regression of tumours and normalisation of serum chromogranin A
Author(s) -
Fossmark R.,
Sørdal Ø.,
Jianu C. S.,
Qvigstad G.,
Nordrum I. S.,
Boyce M.,
Waldum H. L.
Publication year - 2012
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12090
Subject(s) - gastrin , medicine , chromogranin a , gastroenterology , tolerability , atrophic gastritis , endocrinology , gastritis , enterochromaffin like cell , gastrinoma , somatostatin , stomach , antagonist , gastric acid , adverse effect , receptor , immunohistochemistry , secretion
Summary 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 ( YF 476) 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 .