Men with high grade prostatic intraepithelial neoplasia (HG PIN) on prostate biopsy are at high risk for prostate cancer (PCA). The ability to reverse HG PIN, a precursor of PCA, may reduce the incidence or delay the development of PCA. ACAPODENE ™ (toremifene) is a selective estrogen receptor modulator (SERM) that has been shown in preclinical models to both eliminate HG PIN and reduce the incidence of PCA. Toremifene was evaluated for safety and efficacy in men diagnosed with HG PIN. An open labeled, Phase IIa clinical trial enrolled 21 men (mean age 64.7 years) who had HG PIN only on biopsy within 6 mo ofentry into the study. From those men, 18 (86%) completed toremifene treatment (60 mg/day PO for 4 mo) followed by a prostate biopsy to determine HG PIN status. Serum prostate specific antigen (PSA), % free PSA, testosterone (T), estradiol (E2), and quality of life were measured. Following toremifene treatment, 72% of the HG PIN men compared to 17.9% of historical controls had no HG PIN on subsequent prostate biopsies. Mean PSA was trended higher and % free PSA was elevated. Quality oflife was not significantly affected, and there were no serious adverse events. Toremifene appears to reduce HG PIN, and was well tolerated in this small, exploratory trial. A double blind, dose finding, randomized, and placebo controlled Phase IIb/III study is currently in progress in 516 men with HG PIN to further study toremifene's activity against PCA incidence.

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