Treatment of gastric carcinoids type 1 with the gastrin receptor antagonist netazepide (YF476) results in regression of tumours and normalisation of serum chromogranin A R. Fossmark* ,† , Ø. Sørdal † , C. S. Jianu* † , G. Qvigstad* ,† , I. S. Nordrum ‡,§ , M. Boyce ¶ & H. L. Waldum* ,† *Department of Gastroenterology and Hepatology, St. Olavs Hospital, Trondheim, Norway. † Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. ‡ Department of Laboratory Medicine, Children’s and Women’s Health, Faculty of Medicine, NTNU, Medisinsk teknisk forskningssenter, Trondheim, Norway. § Department of Pathology and Medical Genetics, St. Olav’s Hospital, Erling Skjalgssonsgate 1, Trondheim, Norway. ¶ Hammersmith Medicines Research, London, UK. Correspondence to: Dr R. Fossmark, Department of Gastroenterology and Hepatology, St. Olavs Hospital, Prinsesse Kristinas Gate 1, 7006 Trondheim, Norway. E-mail: reidar.fossmark@ntnu.no Publication data Submitted 27 August 2012 First decision 7 September 2012 Resubmitted 23 September 2012 Accepted 27 September 2012 EV Pub Online 16 October 2012 SUMMARY Background Patients with chronic atrophic gastritis have long-term gastric hypoacidity, and secondary hypergastrinaemia. Some also develop gastric ECL cells car- cinoids (type 1 GC). Most type 1 GC remain indolent, but some metastas- ise. 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-depen- dent. Controlled studies and long-term treatment are justified to find out whether netazepide treatment can eradicate type 1 gastric carcinoids. Aliment Pharmacol Ther 2012; 36: 1067–1075 ª 2012 Blackwell Publishing Ltd 1067 doi:10.1111/apt.12090 Alimentary Pharmacology and Therapeutics