Effect of a high dosage of ketoconazole all or not combined with ovariectomy on N-nitroso-N-methylurea-induced mammary cancer in the rat.
Rats bearing mammary carcinomas induced by N-nitroso-N-methylurea (NMU) were subjected to either no treatment (C), to ovariectomy (O), to continuous ketoconazole dosing at 400 ppm into the diet (K) or to both ovariectomy and ketoconazole dosing (O + K). In both C and K groups survival over the experimental period of 15 weeks was low (12.5% and 15.8%, respectively). In the O group and the O + K group survival markedly improved (52.6%, P less than 0.05 and 68.4%, P less than 0.01, respectively) and partial or complete tumor regression was noted respectively in 2 and 8 rats out of 19. Whereas C and K dosed groups showed an equally high tumor multiplicity and fast tumor growth, both parameters were markedly reduced in the O group and more markedly reduced in the O + K group which showed an overall decrease of the number of tumors. These findings indicate a synergistic effect of ketoconazole dosing and ovariectomy.
D000818:Animals; D002369:Castration; D003131:Combined Modality Therapy; D005260:Female; D007654:Ketoconazole / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000628:therapy*; D008770:Methylnitrosourea; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D008770:Methylnitrosourea; D007654:Ketoconazole