SOMATOSTATIN ANALOG OCTREOTIDE ENHANCES THE ANTINEOPLASTIC EFFECTS OFTAMOXIFEN 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 endocri ne therapies and by the fact that initially responding tumors often es cape 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 m odels, on the antineoplastic actions of tamoxifen and ovariectomy on 7 ,12-dimethylbenz(a)anthracene-induced mammary tumors. Rats received ta moxifen (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 ani mal and the sum of the volumes of palpable tumors per animal were sign ificantly less in the combination treatment than in the others. In ova riectomized rats the marked regression of established tumors in the in itial 4 weeks after ovariectomy was frequently followed by tumor regro wth. However, continuous infusion of octreotide (50 mu g/kg/h for 6 we eks postovariectomy) significantly (P < 0.01) suppressed this regrowth . Our data suggest that octreotide enhances the antitumor effects of t amoxifen or ovariectomy in the 7,12-dimethylbenz(a)anthracene mammary cancer model.