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


OBJECTIVE
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.
Department of Gastroenterology and Hepatology, St. Olavs Hospital, Trondheim, Norway. reidar.fossmark@ntnu.no
R
R
Fossmark
Ø
Ø
Sørdal
C S
CS
Jianu
G
G
Qvigstad
I S
IS
Nordrum
M
M
Boyce
H L
HL
Waldum
D000368:Aged; D001570:Benzodiazepinones / Q000627:therapeutic use*; D002276:Carcinoid Tumor / Q000097:blood / Q000188:drug therapy*; D053379:Chromogranin A / Q000097:blood*; D005260:Female; D005755:Gastrins / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors*; D013274:Stomach Neoplasms / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
D001570:Benzodiazepinones; D053379:Chromogranin A; D005755:Gastrins; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; C104428:YF 476