Development of resistance to a long-acting somatostatin analogue during treatment of two patients with metastatic endocrine pancreatic tumours

Abstract

Two patients with metastatic endocrine pancreatic tumours intially responded well to therapy with the long-acting somatostatin analogue SMS 201-995. In the first patient with a n insulinoma both the number of hypoglycemic attacks and the increased insulin levels decreased intially, but returned to pretreatment intensity and concentrations within 9 days after the start of therapy with 200-300 .mu.g SMS 201-995 daily. After a short interruption, no effect was observed of re-institution of therapy at a dose of 400 .mu.g SMS 201-995 daily. In the other patient with a metastatic vipoma both diarrhea, hypokalemia and plasma VIP levels reacted initally well to SMS 201-995 treatment with 300 .mu.g per day, but resistance to therapy developed after 2 weeks. An increase in the dose of the analgoue to maximally 600 .mu.g/day was followed by a transient improvement, but finally both the volume of diarrhea and the levels of vasoactive intestinal polypeptide were higher than those before the start of therapy. Conclusions: Development of resistance to SMS 201-995 both with regard to the clinical effect and to the inhibitory effect on tumour hormone secretion can be expected in some patients with metastatic endocrine pancreatic tumours. On the basis of our clinical observations down-regulation of somatostatin receptors is suggested to be one of the mechanisms of this development.