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

Abstract

BACKGROUND:

We aimed to investigate the safety and efficacy of dutasteride, a 5α-reductase inhibitor, on prostate cancer progression in men with low-risk disease who chose to be followed up with active surveillance.

METHODS:

In our 3 year, randomised, double-blind, placebo-controlled study, undertaken at 65 academic medical centres or outpatient clinics in North America, we enrolled men aged 48-82 years who had low-volume, Gleason score 5-6 prostate cancer and had chosen to be followed up with active surveillance. We randomly allocated participants in a one-to-one ratio, stratified by site and in block sizes of four, to receive once-daily dutasteride 0·5 mg or matching placebo. Participants were followed up for 3 years, with 12-core prostate biopsy samples obtained after 18 months and 3 years. The primary endpoint was time to prostate cancer progression, defined as the number of days between the start of study treatment and the earlier of either pathological progression (in patients with ≥1 biopsy assessment after baseline) or therapeutic progression (start of medical therapy). This trial is registered with ClinicalTrials.gov, number NCT00363311.

FINDINGS:

Between Aug 10, 2006, and March 26, 2007, we randomly allocated 302 participants, of whom 289 (96%) had at least one biopsy procedure after baseline and were included in the primary analysis. By 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, 95% CI 0·43-0·89; p=0·009). Incidence of adverse events was much the same between treatment groups. 35 (24%) men in the dutasteride group and 23 (15%) controls had sexual adverse events or breast enlargement or tenderness. Eight (5%) men in the dutasteride group and seven (5%) controls had cardiovascular adverse events, but there were no prostate cancer-related deaths or instances of metastatic disease.

INTERPRETATION:

Dutasteride could provide a beneficial adjunct to active surveillance for men with low-risk prostate cancer.

FUNDING:

GlaxoSmithKline.

• Authors: Neil E Fleshner, M Scott Lucia, Blair Egerdie, Lorne Aaron, Gregg Eure, Indrani Nandy, Libby Black, Roger S Rittmaster
• Journal: Lancet (London, England) (Lancet) Vol. 379 Issue 9821 Pg. 1103-11 (Mar 24 2012) ISSN: 1474-547X [Electronic] England
• PMID: 22277570 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• 5-alpha Reductase Inhibitors
• Azasteroids
• Prostate-Specific Antigen
• Dutasteride

Topics

• 5-alpha Reductase Inhibitors (administration & dosage, therapeutic use)
• Aged
• Aged, 80 and over
• Anxiety (epidemiology)
• Azasteroids (administration & dosage, therapeutic use)
• Disease Progression
• Double-Blind Method
• Dutasteride
• Female
• Humans
• Male
• Middle Aged
• Proportional Hazards Models
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (drug therapy, pathology, psychology)
• Surveys and Questionnaires