PRECLINICAL STUDIES ON THE ANTICANCER ACTIVITY OF THE SOMATOSTATIN ANALOG OCTREOTIDE (SMS 201-995)

The antiproliferative effect of somatostatin-14 and its analog octreot ide on in vitro pancreatic and breast tumor cells has led to the sugge stion that octreotide may have further oncological indications in addi tion to gastroenteropancreatic tumors. To extend these in vitro observ ations, we evaluated the effect of octreotide in rodent models of panc reatic and breast tumors. Octreotide of 5 or 50 mug b.i.d. in nude mic e bearing solid MiaPaCa pancreatic tumors (subline 21) or ZR-75-1 brea st tumors induced significant inhibition of tumor growth from week 2 u ntil the end of treatment at week 5. After 5 weeks the mean volume of ZR-75-1 tumors in animals treated with the 50-mug regimen was 48% that of control. Autoradiographic studies showed a high percentage (71%) o f ZR-75-1 tumors to be somatostatin receptor-positive. In addition, th e growth of ZR-75-1 cells in vitro was significantly inhibited by octr eotide. The drug was also tested in a second breast cancer model, DMBA -induced mammary tumors in rats, and continuous administration of 10 m ug/kg/h over 6 weeks led to an approximately 50% reduction in the numb er of tumors arising in the rat mammary gland. These data suggest that pancreatic and breast cancer may be among the malignant diseases clin ically susceptible to octreotide.