Dutasteride for the prevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia: results of a phase III randomized open-label 3-year trial

Milonas, Daimantas; Auškalnis, Stasys; Skulčius, Giedrius; Gudinavičienė, Inga; Jievaltas, Mindaugas; Joniau, Steven

doi:10.1007/s00345-016-1938-8

Cited by 6 publications

(7 citation statements)

References 23 publications

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“…With the primary end cancer-free survival (CFS), per-protocol prostate biopsies were performed at 6, 12, 24, and 36 months till completion of the study period of 3-years. The 3-year PCa-free survival was observed to be 43.6% in the surveillance and 49.6% in that of dutasteride group and conclusion was drawn that it did not lower the PCa detection rate, but did not worsen detected PCa characteristics in men with HGPIN [43].…”

Section: Dutasteridementioning

confidence: 86%

5α- Reductase Inhibitors in Prostate Cancer: An Overview

Passi¹

2017

Austin J Cancer Clin Res

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Prostate cancer is the noncutaneous malignancy of the prostate gland in elderly men. Steroid 5α-reductase (5AR) enzyme dictates the cellular availability of dihydrotestosterone to prostatic epithelial cells and consequently modulates its growth. Excessive production of DHT has been implicated in the pathogenesis of Prostate cancer. Finasteride and Dutasteride, clinically available 5AR inhibitors may play an important role in the prevention and treatment of prostate cancer by blocking peripheral conversion of T into DHT. This article gives a brief account of biology of prostate, rationale and efficacy of 5AR inhibitors in prostate cancer management and their associated controversies.

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Section: Dutasteridementioning

confidence: 86%

5α- Reductase Inhibitors in Prostate Cancer: An Overview

Passi¹

2017

Austin J Cancer Clin Res

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“…Agents targeted on hormonal imbalance summarized in this study include Dutasteride [13], Flutamide [14], Bicalutamide [16, 17] and Toremifene [3, 15]. The Dutasteride clinical trial involved in this study showed that Dutasteride did not decrease prostate cancer incidence but did not worsen the HGPIN [13]. In the Flutamide trial, no evidence of benefit was found [14].…”

Section: Discussionmentioning

confidence: 99%

“…But this subgroup setting is not thorough due to the limited biological significance. Recent data showed that a high prostate cancer detection rate at early repeat biopsy (6 months) in men with HGPIN is common in several clinical trials, because prostate cancer has been already present at the initial HGPIN diagnosis [13]. This may help to explain the reason why 6 month intervention showed limited chemoprevention effects.…”

Section: Discussionmentioning

confidence: 99%

“…Estrogen promoted the prostate cancer development by mediating estrogen receptors (ER) [12]. 5-α-reductase inhibitor Dutasteride, Finasteride, AR antagonist Flutamide, Bicalutamide and ER blocker Toremifene are investigated as chemoprevention agents for prostate cancer in clinical trials [2, 3, 13–17]. Due to the anti-oxidant and anti-proliferation activity and the limited toxicities, natural food compounds Selenium, Vitamin E, soy diets, tomato and green tea have been considered as the ideal candidate chemoprevention agents for prostate cancer in clinical trials [8, 18–23].…”

Section: Introductionmentioning

confidence: 99%

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Chemoprevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia (HGPIN): a systematic review and adjusted indirect treatment comparison

Cui

et al. 2017

Oncotarget

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BackgroundHigh-grade prostatic intraepithelial neoplasia (HGPIN) is the precursor or premalignant form of prostate cancer. At least 30% patients with a confirmed HGPIN will develop prostate cancer within 1 year after repeated biopsy. HGPIN patients are the appropriate at-risk population for chemoprevention strategies investigation against prostate cancer. However the commonly used chemoprevention agents that targeted on hormonal imbalance or lifestyle-related factors showed varied results in HGPIN patients.MethodsLiterature searches were conducted in PubMed, EMBASE and Cochrane library according to Cochrane guidelines before January 31st, 2017. Direct meta-analysis were performed to summarize the efficacy of candidate chemopreventative agents Dutasteride, Flutamide, Toremifene, Selenium, Green tea components, Lycopene and natural food products combination. Adjusted indirect meta-analyses were employed to compare the relative efficacy of these candidate chemoprevention agents head-to-head.ResultsThe overall incidence of prostate cancer in HGPIN was slightly decreased by chemoprevention agents (25.7% vs 31.5%, RR = 0.92, 95% CI: 0.83-1.03, P = 0.183), with minor heterogeneity (I2 = 22.3%, χ2 = 15.08, P = 0.237), but without statistical significance. Subgroup analysis showed that green tea catechins significantly decreased prostate cancer in HGPIN patients (7.60% vs 23.1%, RR = 0.39, 95% CI: 0.16-10.97, P P = 0.044), with moderate heterogeneity (I2 = 47.9%, χ2 = 1.92, P = 0.166). The adjusted indirect meta-analysis favored green tea catechins over other chemoprevention agents, and significantly when compared to natural food products combination (RR = 0.355, 95% CI: 0.134-0.934).ConclusionThe overall efficacy of chemoprevention agents in HGPIN patients is limited. But Green tea catechins showed the superiority to decrease prostate cancer in HGPIN patients.

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“…However, without being able to localize the HGPIN, we will most likely need to develop a chemopreventive strategy based an improved understanding of the pathogenesis of the disease. Although HGPIN can be reduced in extent by androgen deprivation manipulations (Bostwick et al 2014;Cui et al 2017), it is unlikely that androgen deprivation approaches will be implemented for such a process, given the known problems (e.g., an excess of higher grade cases in the finasteride and dutasteride treatment groups 7 ) with prostate cancer prevention trials using 5α-reductase inhibitors (Thompson et al 2003;Andriole et al 2010) and the lack of cancer reduction in a recent randomized phase III trial of men with HGPIN by dutasteride (Milonas et al 2017). Also, ideally, we also need to develop a better understanding of which HGPIN lesions have potential to progress to clinically aggressive invasive adenocarcinomas and which do not (Haffner and Barbieri 2016).…”

Section: How To Develop Strategies For Chemoprevention Of Prostate Ca...mentioning

confidence: 99%

Molecular Pathology of High-Grade Prostatic Intraepithelial Neoplasia: Challenges and Opportunities

Trabzonlu

Kulaç

Zheng

et al. 2018

Cold Spring Harb Perspect Med

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A better understanding of the early stages of prostate cancer initiation, potentially arising from precursor lesions, may fuel development of powerful approaches for prostate cancer prevention or interception. The best-known candidate for such a precursor lesion has been referred to as high-grade prostatic intraepithelial neoplasia (HGPIN). Although there is significant evidence supporting the notion that such HGPIN lesions can give rise to invasive adenocarcinomas of the prostate, there are also numerous complicating considerations and evidence that cloud the picture in many instances. Notably, recent evidence has suggested that some fraction of such lesions that are morphologically consistent with HGPIN may actually be invasive carcinomas masquerading as HGPIN-a state that we term "postinvasive intraepithelial carcinoma" (PIC). Although the prevalence of such PIC lesions is not fully understood, this and other factors can confound the potential of identifying prostate precursors that can be targeted for disease prevention, interception, or treatment. Here, we review our current understanding of the morphological and molecular pathological features of prostate cancer precursor lesions.

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Dutasteride for the prevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia: results of a phase III randomized open-label 3-year trial

Abstract: Dutasteride 0.5 mg for 3 years did not lower the PCa detection rate but did not worsen detected PCa characteristics in men with HGPIN.

Cited by 6 publications

References 23 publications

5α- Reductase Inhibitors in Prostate Cancer: An Overview

5α- Reductase Inhibitors in Prostate Cancer: An Overview

Chemoprevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia (HGPIN): a systematic review and adjusted indirect treatment comparison

Molecular Pathology of High-Grade Prostatic Intraepithelial Neoplasia: Challenges and Opportunities

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