EFFECTS OF SANDOSTATIN, ALONE AND IN COMBINATION WITH SURGICAL CASTRATION, ON PANCREATIC CARCINOGENESIS IN RATS AND HAMSTERS

In a previous short-term study (4 months) we found that Sandostatin, w hen administered prophylactically, inhibited growth of putative pre-ne oplastic ductular lesions induced in hamster pancreas by N-nitrosobis( 2-oxopropyl)amine (BOP), but not of acinar lesions induced in rat panc reas by azaserine. The present long-term (12 months) study was carried out to investigate the effects of Sandostatin (3 mu g/day), alone and in combination with orchiectomy, on pancreatic carcinogenesis in azas erine-treated rats and BOP-treated hamsters. In order to mimic therapy in humans, treatment of the animals started 4 months after the last i njection with carcinogen, when (pre)neoplastic lesions had already dev eloped. After treatment with Sandostatin for 8 months, rats developed fewer pancreatic atypical acinar cell nodules and tumours than those n ot treated with Sandostatin. Moreover, multiplicity of (pre)neoplastic acinar lesions was also lower in orchiectomized rats than in intact r ats. However, Sandostatin treatment did not enhance the inhibitory eff ect of surgical castration on pancreatic carcinogenesis in rats. In ha msters that were both orchiectomized and treated with Sandostatin, the development of borderline lesions was significantly inhibited, wherea s such an effect was not present in hamsters that were either surgical ly castrated or treated with Sandostatin alone. In Sandostatin-treated hamsters a significantly lower number of microcarcinomas was found th an in hamsters not treated with Sandostatin. The present findings sugg est that Sandostatin, particularly in combination with surgical castra tion, might be of therapeutic value for treatment of ductular pancreat ic tumours. (C) 1996 Wiley-Liss, Inc.