Topical toremifene: a new approach for cutaneous melanoma?
The distribution of topically applied toremifene (0.5-1 mg/day for 5 days) in the ultraviolet B (UVB)-induced Monodelphis domestica opossum melanoma model was examined. The mean concentration of toremifene measured in the skin was 1200 nmol/g, or > 500 times that detected in any other tissues (blood, brain, liver, testicles, heart, uterus, eyes). In plasma, toremifene could be detected in only one animal of six (0.04 nmol/ml). Intraperitoneal administration of 0.5 mg toremifene daily for 5 days in three female animals resulted in a mean uterus concentration of 22.9 nmol/g, or 400-fold that achieved by topical administration of 0.5 mg/day in three other female Monodelphis (0.05 nmol/g). The cytostatic effect of toremifene was studied in three human melanoma cell lines and three experimental cell lines derived from UVB-induced melanocytic nevi in M. domestica. Toremifene had a cytostatic effect on all cell lines (50% growth-inhibitory concentrations, 5.8-9.6 microM). Topical toremifene administration yields high local concentration with minimal systemic distribution. In addition, toremifene has a cytostatic effect at achievable concentrations in a variety of melanomatous cell lines.
Maenpaa
J
J
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
Dooley
T
T
Wurz
G
G
VandeBerg
J
J
Robinson
E
E
Emshoff
V
V
Sipila
P
P
Wiebe
V
V
Day
C
C
DeGregorio
M
M
D000287:Administration, Topical; D000818:Animals; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D008545:Melanoma / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009893:Opossums; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D017312:Toremifene / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014466:Ultraviolet Rays
D017312:Toremifene