Combined and sequential treatment using FCE 21336, a new prolactin-lowering drug, and medroxyprogesterone acetate (MPA) in DMBA-induced tumors in rats

Abstract

The effect of the new, prolactin-lowering ergoline derivative FCE 21336 and medroxyprogesterone acetate (MPA) given alone and in combination was tested on DMBA-induced mammary tumors in rats. FCE 21336 (0.05 and 0.4 mg/kg p.o.) and MPA (25 and 50 mg/kg s.c.), administered 5 days/week for 4 weeks, inhibited the growth of established tumors and reduced serum prolactin levels. Combined treatment inhibited tumor growth more than single treatment. These results were confirmed in a second experiment: the antitumor effect of the combination of FCE 21336 (0.1 mg/kg p.o.) and MPA (50 mg/kg s.c.) was greater than that of the single treatment and was similar to the effect of ovariectomy. In this experiment rats with tumors that did not respond to 4 weeks' treatment with FCE 21336 (0.1 mg/kg p.o.) were treated during the next 4 weeks with MPA (50 mg/kg s.c.). MPA was effective on FCE 21336-unresponsive tumors. These data indicate that combined FCE 21336 and MPA treatment is more effective than single treatment and that MPA is effective on tumors not sensitive to the prolactin-lowering drug.