Source: DGNews  |  Posted 2 years ago

By Chris Berrie

BARCELONA, Spain -- December 1, 2009 -- Dutasteride significantly reduces the
risk of biopsy-detectable prostate cancer compared with placebo in European men
at increased risk of developing this disease, a benefit that is not associated
with development of high-grade tumours.

Peter Hammerer, MD, Academic Hospital, Braunschweig, Germany, presented this
European subanalysis from the randomised, double-blind, phase 3 global REDUCE
(Reduction by Dutasteride of Prostate Cancer Events) study here on November 27
at the 2nd European Multidisciplinary Meeting on Urological Cancers (EMUC).

The aim of this subanalysis was to determine whether the benefits of the type 1
and type 2 5-alpha-reductase inhibitor dutasteride are confirmed at the
pan-European level.

Eligible subjects were at increased risk for prostate cancer, aged 50-75 years,
had a serum prostate-specific antigen (PSA) 2.5-10 ng/mL (50-60 years) or
3.0-10 ng/mL (>60 years), and had a single negative biopsy on 6-12 cores within
the prior 6 months.

The main exclusion criteria were more than 1 prior negative prostate biopsy,
evidence of high-grade prostatic intraepithelial neoplasia (HG-PIN), or
evidence of atypical small acinar proliferation (ASAP), and a prostate volume
>80 cm³.

In the main REDUCE trial, randomisation was to placebo or dutasteride 0.5 mg
daily; for this European subanalysis, these groups included the efficacy
populations of 2,507 and 2,476 men, respectively.

The primary endpoint was occurrence of biopsy-detectable prostate cancer after
2 and 4 years of treatment. Thus, with a negative biopsy before, and 2-year and
4-year prostate biopsies, Dr. Hammerer noted, “This is an important study
because it really tells us what is going on.”

Secondary endpoints included Gleason score at diagnosis and HG-PIN or ASAP on
biopsy, with benign prostatic hyperplasia (BPH)-related endpoints, and
development of acute urinary retention (AUR) and urinary tract infection (UTI).

The baseline characteristics of the 2 treatment groups were not significantly
different, including for family history of prostate cancer (10% vs 9%), mean
age (63.3 vs 63.3 years), total PSA (6.13 vs 6.12 ng/mL), prostate volume (45.4
vs 45.4 cm³), and International Prostate Symptom Score (IPSS;
8.8 vs 9.0).

With 569 and 426 prostate cancers detected for the placebo and dutasteride
groups, respectively, this demonstrated a significant relative risk reduction
(RRR) for active treatment (years 1-2: 24.9%, 95% confidence interval [CI],
13.4%-34.9%; years 3-4: 24.0%, 95% CI, 7.1%-37.9%; P < .0001).

Compared with placebo, active treatment also showed significantly lower risks
for (respectively) HG-PIN (5.4% vs 3.5%; RRR, 34%; P = .0053), ASAP
(5.1% vs 3.6%; RRR, 28%; P = .0274), AUR (7.1% vs 1.4%; RRR, 80.4%;
P < .0001), BPH-related surgery (5.7% vs 1.4%; RRR 75.6%;
P < .0001), and UTI (9.6% vs 5.8%; RRR, 40.8%; P < .0001).

Similarly, there were significant reductions for mean prostate volume (18.7%
increase vs 16.9% decrease; P < .0001) and IPSS (+1.14 vs -0.6;
P < .0001), and slightly fewer high-grade tumours (Gleason score,
7-10) in the dutasteride group (7.5% vs 7.0%).

These benefits were accompanied by significantly more frequent
dutasteride-related adverse events (12% vs 19%; P < .0001), with
dutasteride treatment showing increased frequencies of decreased libido (2.8%
vs 5.5%), impotence (7.7% vs 10.9%), ejaculation disorders (0.5% vs 2.4%), and
breast disorders (1.9% vs 3.5%).

Finally, Dr. Hammerer noted, “So, if a man is interested in prevention of
prostate cancer, he should be informed about these results so that he has the
option to go for this.”

Funding for this study was sponsored by GlaxoSmithKline.

EMUC was co-organised by the European Association of Urology (EAU), the
European Society for Medical Oncology (ESMO), and the European Society for
Therapeutic Radiology and Oncology (ESTRO).

Presentation title: Dutasteride Lowers the Risk of Biopsy-Detectable
Prostate Cancer Among Men at Increased Risk: European Sub-Analysis From the
Global REDUCE Study. Abstract P082