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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Abstract

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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