SOMATOSTATIN ANALOG OCTREOTIDE ENHANCES THE ANTINEOPLASTIC EFFECTS OF TAMOXIFEN AND OVARIECTOMY ON 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED RAT MAMMARY CARCINOMAS

The efficacy of tamoxifen and ovariectomy in the management of breast cancer is limited by the resistance of many neoplasms to these endocrine therapies and by the fact that initially responding tumors often escape from control during long-term treatment. We evaluated the effect of coadministration of the somatostatin analogue octreotide, which has single agent activity in several in vivo and in vitro breast cancer models, on the antineoplastic actions of tamoxifen and ovariectomy on 7,12-dimethylbenz(a)anthracene-induced mammary tumors. Rats received tamoxifen (0.5 mg/kg twice weekly s.c.), octreotide (10 mu g/kg/h for 6 weeks by osmotic minipump), or the combination 7 weeks following 7,12-dimethylbenz(a)anthracene administration, The number of tumors per animal and the sum of the volumes of palpable tumors per animal were significantly less in the combination treatment than in the others. In ovariectomized rats the marked regression of established tumors in the initial 4 weeks after ovariectomy was frequently followed by tumor regrowth. However, continuous infusion of octreotide (50 mu g/kg/h for 6 weeks postovariectomy) significantly (P < 0.01) suppressed this regrowth. Our data suggest that octreotide enhances the antitumor effects of tamoxifen or ovariectomy in the 7,12-dimethylbenz(a)anthracene mammary cancer model.