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    • During the year study period of men in the dutasteride

    2024-02-09

    During the 4-year study period, 19.9% of men in the dutasteride group developed prostate cancer as compared to 25.1% in the placebo group, which represents an absolute risk endothelin receptor of 5.1% for men taking dutasteride (P<0.001). The rate of prostate cancer detection at biopsy was lower in all subgroups for those receiving dutasteride, including groups based on age, family history of prostate cancer, baseline PSA, baseline TPV, baseline IPSS, or BMI. The reduced incidence occurred primarily in men with tumors having Gleason scores of 5–6. During the first two years of the study, there was no significant difference in incidence of tumors with Gleason score of 8–10 between the placebo and dutasteride groups, but in years 3–4, only 1 tumor with a Gleason score of 8–10 was detected in the placebo group, while 12 were found in the dutasteride group. The authors of this study have speculated that this may be a reflection of the drop-out rate of men in the placebo group who developed cancers in the first two years, leading to a lower number of high grade tumors detected in this group. If, for example, the men in the placebo group who developed tumors with a Gleason score of 5–7 during the first two years of the study had remained in the study until the end (against protocol), a number of these tumors might have been upgraded to high-grade in years 3–4, reducing the differences between the two groups at the 4 year end-point. The REDUCE study also examined the effects of dutasteride on BPH using IPSS, change in TPV from baseline, number of men progressing to surgical intervention, and evidence of BPH-related AUR or urinary tract infection. In this study, as in previous studies where dutasteride was tested in subjects with BPH (ARIA3001, ARIA3002, ARIA3003, EPIC, and CombAT), dutasteride reduced the rate of BPH progression. Upon completion of the REDUCE trial, it was concluded that dutasteride, over a 4 year period, reduced the risk of biopsy-detected cancer and also improved symptoms and reduced progression of BPH. Thus, dutasteride may be considered as a treatment option for men who have been determined to be at a higher risk of developing prostate cancer. These two studies represent important efforts to determine the efficacy of using 5ARIs in prostate cancer risk reduction and disease prevention and have demonstrated that both finasteride and dutasteride can prevent or delay the emergence of prostate cancer [39]. Since completion and analysis of the studies, the use of 5ARIs to reduce the risk of prostate cancer has not yet been universally adopted; the benefits of therapy should be weighed against the prospect of undesirable sexual side effects and decreased quality of life. Recommendations in statements issued by the American Urological Association (AUA) and the American Society of Clinical Oncology (ASCO) ask that physicians discuss the risks and benefits of preventive therapy using 5ARIs with their patients so they can make an informed decision [36].
    5ARIs in the treatment of prostate cancer A natural extension of studies demonstrating the efficacy of using 5ARIs in prevention of prostate cancer is to examine the use of these inhibitors in the treatment of prostate cancer. Expression of both 5AR-1 and -2 are increased in hyperplastic prostate tissue and 5AR-1 expression is increased in prostate cancer as compared to BPH [3], [33]. 5AR-2 expression has been shown to be lower in prostate cancer than in normal tissue [40]. Pre-clinical studies have demonstrated that inhibition of 5AR isoenzymes by finasteride or dutasteride can kill prostate cancer cells and increase apoptosis in vitro[41], [42], [43] and in vivo[44], [45], [46], [47]. The first clinical trial examining the use of finasteride in patients after radical prostatectomy was performed in 1995 and demonstrated that a regimen of 10mg/d finasteride for 1 year delayed the increase in serum PSA for approximately 9 months as compared to placebo [48]. The results of this study indicated that treatment with a 5ARI delays, but does not prevent, a rise in serum PSA after radical prostatectomy.