THE EFFECT OF THE SOMATOSTATIN ANALOG SMS-201-995 ON EXPERIMENTAL PANCREATIC CARCINOGENESIS IN THE SYRIAN GOLDEN-HAMSTER

Somatostatin analogues have been suggested as possible therapy for human pancreatic cancer. This paper investigates the effect of the somatostatin analogue SMS 201-995 (Sandoz) in the Syrian golden hamster model of nitrosamine-induced pancreatic carcinogenesis. Step-wise increasing doses of i.v. SMS 201-995 suppressed pancreatic juice output from a median basal value of 212 mg/kg body wt/h (Q1:Q3 = 121:334) to a median basal value of 70 mg/kg body wt/h during infusion of 5-mu-g/kg body wt/h of SMS 201-995 (Q1:Q3 = 64:102, P < 0.05). Chronic s.c. injection of 5 and 10-mu-g/kg body wt SMS 201-995 twice daily for 3 days each week, did not affect pancreatic wet wt or pancreatic total DNA content after 1 or 6 weeks of treatment when compared to controls. The most interesting and unexpected finding in our study was that SMS 201-995 seemed to promote pancreatic carcinogenesis when administered in low dosage. More SMS 201-995 treated animals receiving 5-mu-g/kg body wt developed invasive pancreatic adenocarcinoma than controls after 15 weeks of carcinogen (4/10 animals versus 0/10, P < 0.05, Fisher's exact test) and pancreatic involvement by tumour was more extensive (17/75 pancreatic blocks affected versus 0/71, P < 0.001). When carcinoma in situ and microcarcinomata were analysed with invasive lesions, animals injected with 5-mu-g/kg body wt SMS 201-995 were still significantly more affected than controls (33/75 blocks versus 9/71, P < 0.001). Hamsters injected with the higher SMS 201-995 dose (10-mu-g/kg body wt) did not show any increase in malignancy over the controls. These results suggest that the effect of SMS 201-995 on pancreatic carcinogenesis in the Syrian hamster is complex and varies with dose administered. Further work is required before its use on man can be justified.