New specific long-acting somatostatin analogues in the treatment of pancreatic endocrine tumours

Somatostatin is a powerful inhibitor of pancreatic hormones. Its therapeutic uses for endocrine tumours has been impeded by its lack of specificity and very short action of only a few minutes. We have used three recently developed selective analogues in patients with functioning metastatic gastrinomas, PPomas, glucagonomas and VIPomas. D Try⁸ D Cys¹⁴ somatostatin infused intravenously at 8 μg/min caused marked hormone suppression. In a PP/VIPoma case, for example, mean basal VIP fell from 198 ± 6 to 43 ± 3 pmol/l while PP fell from 403 ± 14 to 52 ± 3 pmol/l. In a glucagonoma, also producing PP, glucagon fell from 1800 ± 26 to 282 ± 13 pmol/l while PP fell from 21 ± 0.3 to 6.4 ± 0.2 nmol/l. D Try⁸ and D Try⁸ D Cys¹⁴, Des^{1,2,4,5,12,13} Des¹,²,⁴,⁵,^b12,¹3 somatostatin analogues had a dramatic prolongation of effect. A single 2 mg subcutaneous dose suppressed glucagon 65% for 3 hours, with a resulting reduction in hyperglycaemia. A larger dose (5 or 10mg) resulted in greater hormone suppression (<80%), which was well maintained for over 12 hours. No side effects were noted. Thus all three analogues appear effective in suppressing tumour hormone production. The new long-acting analogues were active for at least 12 hours and, being effective by twice daily subcutaneous injections, offer a new therapeutic approach for the treatment of endocrine tumours and perhaps other hormone excess states.