TOPICAL TOREMIFENE - A NEW APPROACH FOR CUTANEOUS MELANOMA

The distribution of topically applied toremifene (0.5-1 mg/day for 5 d ays) in the ultraviolet B (UVB)-induced Monodelphis domestica opossum melanoma model was examined. The mean concentration of toremifene meas ured in the skin was 1200 nmol/g, or >500 times that detected in any o ther 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 fo r 5 days in three female animals resulted in a mean uterus concentrati on 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 cy tostatic effect of toremifene was studied in three human melanoma cell lines and three experimental cell lines derived from UVB-induced mela nocytic nevi in M. domestica. Toremifene had a cytostatic effect on al l cell lines (50% growth-inhibitory concentrations, 5.8-9.6 muM). Topi cal toremifene administration yields high local concentration with min imal systemic distribution. In addition, toremifene has a cytostatic e ffect at achievable concentrations in a variety of melanomatous cell l ines.