Antitumor effects of combination toremifene and medroxyprogesterone acetate (MPA) in vitro and in vivo.
The estrogen (ER) and progesterone (PgR) receptor levels in various gynecological tumors were measured. The same tumors were exposed in vitro to toremifene, MPA or their combination and the growth of the tumors was followed by measuring the adenosine triphosphate (ATP) within the cells by a simple bioluminescence assay. Altogether 34 clinical samples were studied. DMBA-induced mammary tumors bearing rats were treated in vivo with toremifene, MPA and their combination. About half of the ovarian cancers and 6 out of the 7 adenocarcinomas of uteri contained ER. The ovarian tumors were PgR rich in 25% and adenocarcinomas of uteri in 6 out of the 7 cases. When compared to control toremifene (concentration 1 mumol/l) was able to decrease the number of living cells to 50% or less in 9/34 samples, MPA (concentration 10 mumol/l) in 17/34 samples, and the combination in 25/34 samples. In five cases the antitumor effect of the combination was synergistic. In two cases signs of weak antagonism were seen. In vivo the antitumor effect of toremifene and MPA was clearly synergistic against DMBA-induced cancers. The effect was dose-dependent and at sufficiently high doses it was possible to eradicate the tumors and cure the animals.
Kangas
L
L
Farmos Group Ltd, Turku, Finland.
Grönroos
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives; D017258:Medroxyprogesterone Acetate; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives; D017312:Toremifene; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene; D017312:Toremifene; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone