Men with high-grade
prostatic intraepithelial neoplasia (PIN) evident on prostate biopsy are at high risk for the eventual development of
prostate cancer. The ability to reverse high-grade PIN may reduce the incidence or delay the development of
prostate cancer.
Toremifene (GTx-006, Acapodene trade mark ) is a
selective estrogen receptor modulator that has been shown in the transgenic mouse model of
prostate cancer to eliminate high-grade PIN and reduce the incidence of
prostate cancer. This study was aimed at the evaluation of the safety and efficacy of
toremifene in men diagnosed with high-grade PIN. This was an open-label, phase IIA clinical trial that enrolled 21 men (mean age, 64.7 years) with evidence of high-grade PIN on biopsy within 6 months of entry into the study. Eighteen of these men (86%) completed
toremifene treatment (60 mg/day orally for 4 months) and then underwent follow-up prostate biopsy (8 cores) to determine high-grade PIN status. The effect of the
drug on serum
prostate-specific antigen (PSA), percentage of free PSA,
testosterone,
estradiol, and quality of life was also measured. After
toremifene treatment, 72% of these 18 men (vs. 17.9% of historical controls) had no high-grade PIN on subsequent prostate biopsies. Mean PSA trended higher, and percentage of free PSA was increased. Quality of life was not significantly affected by treatment. There were 3 mild adverse events, and no serious adverse events.
Toremifene appeared to reduce high-grade PIN in this small, exploratory trial. The
drug was well tolerated. A double-blind, dose-finding, randomized, placebo-controlled phase IIB/III study is currently open to further study
toremifene's activity against high-grade PIN and
prostate cancer incidence.