Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial

Fleshner, Neil; Lucia, M. Scott; Egerdie, Blair; Aaron, Lorne; Eure, Gregg; Nandy, Indrani; Black, Libby; Rittmaster, Roger S.

doi:10.1016/s0140-6736(11)61619-x

Cited by 171 publications

(134 citation statements)

References 27 publications

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“…12 The absolute benefit between these 2 groups seems consistent with results from the REDEEM trial. 9 However, drawing any conclusions based on these results are limited by the retrospective nature of this study and its limited sample size. The latter can be attributed primarily to the large number of patients excluded due to insufficient PSA values.…”

Section: Discussionmentioning

confidence: 83%

“…22 For patients with known prostate cancer, the REDEEM trial showed no increase in the number of high-grade cases. 9 Thus, based on more recent data, it seems increasingly unlikely that 5-ARIs cause grade progression.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 One of the few randomized studies that evaluated 5-ARIs in active surveillance patients is the REDEEM (Reduction by Dutasteride of Clinical Progression Events in Expectant Management) trial. 9 A total of 304 favourable-risk patients were randomized to either dutasteride or placebo for 3 years. The intervention arm significantly reduced the risk of disease progression (38% vs. 49%, p = 0.009), which was defined as the initiation of therapy or pathological progression.…”

Section: Introductionmentioning

confidence: 99%

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Utility of 5-alpha-reductase inhibitors in active surveillance for favourable risk prostate cancer

Chiang

Loblaw

Jethava

et al. 2013

CUAJ

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Introduction: This retrospective review compares prostate-specific antigen (PSA) doubling time (DT) prior to the initiation of a 5-alphareductase inhibitor (pre-5-ARI) to after the PSA nadir (post-nadir) has been reached for patients on active surveillance for favourablerisk prostate cancer. Methods: Between 1996 and 2010, a total of 100 men with a history of 5-ARI use were captured from our active surveillance database. Twenty-nine patients had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir DTs. PSADT was calculated using the general linear mixed-model method. Results: The median follow-up was 69.5 months. The median pre-5-ARI PSADT was 55.8 (range: 6-556.8) months, while the post-nadir value was 25.2 (range: 6-231) months (p = 0.0081). Six patients were reclassified after an average of 67.7 (range: 59-95) months, due to progression in PSADT (n = 2) or Gleason score (n = 4). The median pre-5-ARI and post-nadir DTs for this group were 42.3 (range: 32.4-91.1) and 21.1 (range: 6-44.3) months, respectively. Conclusion: 5-ARIs significantly decreased PSADT compared to prior to their initiation. This effect may be due to preferential suppression of benign tissue following PSA nadir. The resulting PSADT would then represent a more accurate depiction of the true cancerrelated DT. If validated with a larger cohort, 5-ARIs may enhance the utility of PSADT as a biomarker of disease progression in active surveillance.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Utility of 5-alpha-reductase inhibitors in active surveillance for favourable risk prostate cancer

Chiang

Loblaw

Jethava

et al. 2013

CUAJ

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“…A retrospective study rejected the results of these clinical trials on PCa prevention and hence these drugs have not been FDA-approved yet for the prevention of PCa [102] . Subsequently, two clinical trials, (in phase II and IV, respectively) showed dutasteride to decrease the incidence of histopathological progression in patients with lowgrade PCa and delay biochemical progression in patients who underwent radical prostatectomy or radiation therapy for localised PCa, respectively [103,104] .…”

Section: Srd5amentioning

confidence: 99%

Androgen-AR axis in primary and metastatic prostate cancer: chasing steroidogenic enzymes for therapeutic intervention

Pippione¹,

Boschi²,

Pors³

et al. 2017

JCMT

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Androgens play an important role in prostate cancer (PCa) development and progression. Although androgen deprivation therapy remains the front-line treatment for advanced prostate cancer, patients eventually relapse with the lethal form of the disease. The prostate tumor microenvironment is characterised by elevated tissue androgens that are capable of activating the androgen receptor (AR). Inhibiting the steroidogenic enzymes that play vital roles in the biosynthesis of testosterone (T) and dihydrotestosterone (DHT) seems to be an attractive strategy for PCa therapies. Emerging data suggest a role for the enzymes mediating pre-receptor control of T and DHT biosynthesis by alternative pathways in controlling intratumoral androgen levels, and thereby influencing PCa progression. This supports the idea for the development of multi-targeting strategies, involving both dual and multiple inhibitors of androgen-metabolising enzymes that are able to affect androgen synthesis and signalling at different points in the biosynthesis. In this review, we will focus on CYP17A1, AKR1C3, HSD17B3 and SRD5A, as these enzymes play essential roles in all the three androgenic pathways. We will review also the AR as an additional target for the design of bifunctional drugs. Targeting intracrine androgens and AKR1C3 have potential to overcome enzalutamide and abiraterone resistance and improve survival of advanced prostate cancer patients.

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“…An obvious inference is that 5-alpha reductase inhibitors may be beneficial in men on surveillance. This was evaluated in a prospective randomized trial [32]; men on surveillance were randomized between dutasteride and placebo for 3 years, and had a mandated biopsy at 18 months and 3 years. At 3 years, 54 (38%) of 144 men in the dutasteride group and 70 (48%) of 145 controls had prostate cancer progression (pathological or therapeutic; hazard ratio 0·62, p = 0·009): 35 (24%) men in the dutasteride group and 23 (15%) controls had sexual adverse events or breast enlargement or tenderness.…”

Section: Role Of 5-alpha Reductase Inhibitorsmentioning

confidence: 99%

Active Surveillance for Low-Risk Prostate Cancer

Klotz

2015

Curr Urol Rep

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Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial

Cited by 171 publications

References 27 publications

Utility of 5-alpha-reductase inhibitors in active surveillance for favourable risk prostate cancer

Utility of 5-alpha-reductase inhibitors in active surveillance for favourable risk prostate cancer

Androgen-AR axis in primary and metastatic prostate cancer: chasing steroidogenic enzymes for therapeutic intervention

Active Surveillance for Low-Risk Prostate Cancer

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