• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.5
• /
• pp.1827-1831
• /
• 2015

Background: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA). Materials and Methods: Six-week-old mice were treated subcutaneously with $50{\mu}g/g$ of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry. Results: CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice. Conclusions: Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.8
• /
• pp.3645-3649
• /
• 2014

The aim of this study was to evaluate the efficacy of third-line combined androgen blockade (CAB) therapy for castration-resistant prostate cancer that relapsed after primary and second-line CAB. We retrospectively reviewed the medical records of 52 patients who received first-, second-, and third-line CAB therapy (medical or surgical castration, plus steroidal antiandrogen of chlormadinone acetate, or nonsteroidal antiandrogen of flutamide or bicalutamide). For cumulative analysis, we searched the PubMed database and identified a total of 50 cases published in English. Including our cases, this provided a total of 102 cases for analysis. In our study cohort, 11 cases (21.2%) achieved more than 50% reduction of serum prostate-specific antigen (PSA) on initiation of third-line CAB. We found that third-line CAB with nonsteroidal antiandrogen after second-line CAB with steroidal antiandrogen exhibited favorable results, with a positive response in six of 13 patients (46.2%). Cumulative analysis findings were comparable. Regarding the timing of third-line CAB administration, 15 patients had started at a PSA equal to or less than 4.0 ng/ml, and eight of them (53.3%) showed a positive response to treatment, compared to only three of 37 patients (8.1%) whose PSA at the initiation of third-line therapy was higher than 4.0 ng/ml (p<0.001). We conclude that third-line CAB with nonsteroidal antiandrogen would be particularly useful for patients whose cancer progressed after second-line CAB with steroidal antiandrogen. The timing of treatment seems to be important because the higher the PSA at the start of third-line therapy, the lower the PSA response rate.