Introduction: In a two-centre, 12-week, open trial in 16 patients with autoimmune chronic atrophic gastritis, hypergastrinaemia, multiple type 1 gastric neuroendocrine tumours (NETs), and raised circulating CgA, the gastrin/CCK2 receptor antagonist (CCK2RA), netazepide, reduced the tumour number and size, and normalised CgA.
Aim(s): To treat those patients with netazepide for longer, and to identify new biomarkers.
Materials and methods: After a mean 14 months off netazepide, 13 patients took it for another 52 weeks. Assessments were: gastroscopy; gene transcript expression in corpus biopsies; and blood CgA, miR-222 and gastrin.
Results: While off treatment, the number and size of the tumours, and CgA all increased again. Netazepide for 52 weeks eradicated all tumours in 5 patients, left one patient with only one tumour, and reduced further the number and size of the tumours in the others, and normalised CgA (P<0.01). Gastrin was unaffected. Netazepide was safe and well tolerated.
Netazepide reduced mRNA abundances of overexpressed CgA, histidine decarboxylase, pappalysin 2 (PAPPA2), glycoprotein hormones alpha polypeptide, and miR-222 in biopsies, and miR-222 in blood (P<0.05). miR-222 targets the tumour suppressor and oncogene p27kip1.
Conclusions: A CCK2RA is a potential medical and targeted treatment for gastric NETs that are gastrin driven, and an alternative to endoscopic resection or surgery. Treatment can be monitored by biomarkers in blood or biopsies. The results justify a multicentre, placebo-controlled trial.
05 Dec 2016
UK and Ireland Neuroendocrine Tumour Society