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The gastrin receptor antagonist netazepide (YF476) in patients with type 1 gastric enterochromaffin-like cell neuroendocrine tumours: review of long-term treatment

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Objective

Netazepide (YF476) is a recently developed, orally active gastrin receptor antagonist that, in short trials in patients with type 1 gastric enterochromaffin-like cell neuroendocrine tumours, has been shown to induce a significant reduction in the number and size of tumours as well as serum chromogranin A (CgA). The aim of this review is to evaluate the long-term effect and safety of netazepide.

Patients and methods

Five patients previously treated with netazepide in an open-label trial were offered continuous treatment with netazepide 25 mg once daily. Upper endoscopy was performed every 6 months. The tumours were counted and measured, and tissue samples were obtained from the flat corpus mucosa. Enterochromaffin-like cell hyperplasia was classified according to Solcia and colleagues and volume density of CgA immunoreactive (IR) cells was calculated. Fasting serum CgA and fasting serum gastrin were measured every 3 months.

Results

All tumours regressed completely in three of five patients; time until total disappearance was 3, 9 and 12 months. In the other two patients, the number of tumours was reduced from 13 to 5 and from 14 to 3. Serum CgA showed a rapid and sustained decrease (P<0.001). The mean reduction in serum CgA was 4.1±0.5 nmol/l. Similarly, volume density of CgA IR cells in the flat corpus mucosa decreased (P<0.001), with the mean change being 2.0±0.4%. Serum gastrin and volume density of gastrin IR cells in the antral part of the stomach remained unchanged (P=0.2 and 0.7, respectively).

Conclusion

Long-term administration of netazepide is effective and safe.
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Keywords: chromogranin A; enterochromaffin-like cell hyperplasia; gastric carcinoids; gastrin receptor antagonist; netazepide; type 1 gastric enterochromaffin-like cell neuroendocrine tumours

Document Type: Research Article

Affiliations: 1: Department of Gastroenterology and Hepatology, Department of Cancer Research and Molecular Medicine, Faculty of Medicine 2: Department of Pathology, St. Olav’s Hospital, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Department of Laboratory Medicine, Children’s and Woman’s Health, Norwegian University of Science and Technology, Trondheim, Norway 3: Department of Gastroenterology and Hepatology 4: Hammersmith Medicines Research, London, UK

Publication date: November 1, 2016

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