Phase IIA clinical trial to test the efficacy and safety of Toremifene in men with high-grade prostatic intraepithelial neoplasia.

Abstract

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.

• Authors: Mitchell S Steiner, Charlie R Pound
• Journal: Clinical prostate cancer (Clin Prostate Cancer) Vol. 2 Issue 1 Pg. 24-31 (Jun 2003) ISSN: 1540-0352 [Print] United States
• PMID: 15046680 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• Toremifene

Topics

• Administration, Oral
• Aged
• Antineoplastic Agents, Hormonal (administration & dosage, adverse effects)
• Biopsy, Needle
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Prognosis
• Prostatic Intraepithelial Neoplasia (drug therapy, mortality, pathology)
• Prostatic Neoplasms (drug therapy, mortality, pathology)
• Quality of Life
• Risk Assessment
• Survival Analysis
• Toremifene (administration & dosage, adverse effects)
• Treatment Outcome