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]
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