A Phase 3, Double-blind, Randomised, Parallel-group, Placebo-controlled Study of Oral Weekly Alendronate for the Prevention of Androgen Deprivation Bone Loss in Nonmetastatic Prostate Cancer: The Cancer and Osteoporosis Research with Alendronate and Leuprolide (CORAL) Study

Abstract Background Androgen-deprivation therapy (ADT) induces loss of bone mineral density (BMD) and increases the risk of fractures in patients with prostate cancer (PCa). We sought to determine whether a weekly dose of alendronate, an oral bisphosphonate, could reduce this unwanted side-effect. O...

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Bibliographic Details
Published in:European urology 2013-05, Vol.63 (5), p.927-935
Main Authors: Klotz, Laurence H, McNeill, Irene Y, Kebabdjian, Marlene, Zhang, Liying, Chin, Joseph L
Format: Article
Language:English
Subjects:
Absorptiometry, Photon
Administration, Oral
Aged
Aged, 80 and over
Alendronate - administration & dosage
Alendronate - adverse effects
Alkaline Phosphatase - blood
Analysis of Variance
Androgen Antagonists - administration & dosage
Androgen Antagonists - adverse effects
Androgen deprivation therapy
Antineoplastic Agents, Hormonal - administration & dosage
Antineoplastic Agents, Hormonal - adverse effects
Biological and medical sciences
Biomarkers - blood
Bisphosphonates
Bone Density - drug effects
Bone Density Conservation Agents - administration & dosage
Bone Density Conservation Agents - adverse effects
Bone health
Bone mineral density
Canada
Chi-Square Distribution
Collagen Type I - blood
Diseases of the osteoarticular system
Double-Blind Method
Drug Administration Schedule
Hip Joint - diagnostic imaging
Hip Joint - drug effects
Humans
Injections, Intramuscular
Leuprolide - administration & dosage
Leuprolide - adverse effects
Lumbar Vertebrae - diagnostic imaging
Lumbar Vertebrae - drug effects
Male
Medical sciences
Middle Aged
Nephrology. Urinary tract diseases
Osteoporosis - blood
Osteoporosis - chemically induced
Osteoporosis - diagnostic imaging
Osteoporosis - prevention & control
Osteoporosis. Osteomalacia. Paget disease
Patient Selection
Peptides - blood
Predictive Value of Tests
Prostate cancer
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - pathology
Time Factors
Treatment Outcome
Tumors of the urinary system
Urinary tract. Prostate gland
Urology
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Summary:Abstract Background Androgen-deprivation therapy (ADT) induces loss of bone mineral density (BMD) and increases the risk of fractures in patients with prostate cancer (PCa). We sought to determine whether a weekly dose of alendronate, an oral bisphosphonate, could reduce this unwanted side-effect. Objective To assess whether once-weekly oral alendronate therapy would maintain or improve BMD in men initiating ADT for localised PCa. Design, setting, and participants A multicentre, double-blind, randomised, placebo-controlled study, we included hormonally naïve PCa patients initiating ADT with leuprolide acetate 30 mg intramuscularly every 4 mo. Intervention Patients were randomised to receive either oral alendronate 70 mg once weekly or placebo for 1 yr. Both groups received daily calcium 1 g and vitamin D 400 international units. Outcome measurements and statistical analysis Changes in BMD (at the lumbar spine [LS] and total hip [TH]) and bone markers. Results and limitations One hundred ninety-one subjects were enrolled, and 186 were randomised between alendronate ( n = 84) and placebo ( n = 102). The alendronate group demonstrated a mean spine BMD increase of 1.7% compared with −1.9% in the placebo group ( p < 0.0001). Alendronate also increased the BMD at the hip (percent change: 0.7%) compared to placebo (−1.6%). Median urinary N-terminal crosslinking telopeptide of type I collagen (Ntx) values decreased by 3.5% in the alendronate group and increased by 16.5% in the placebo arm, even after adjusting for centre ( p = 0.510) and baseline urinary Ntx ( p < 0.0001). Bone-specific alkaline phosphatase (BSAP) decreased a median of 2.25% in the alendronate group and increased a median of 3.12% in the placebo arm, regardless of centre or baseline BSAP or other covariates ( p < 0.0001). The safety and tolerability profile was similar for the two treatment groups. Conclusions Although the study was closed early because of slow accrual, it showed that weekly oral alendronate prevented bone loss and increased bone mass in addition to decreasing bone turnover in patients initiating ADT for localised PCa, with few related side-effects.
ISSN:0302-2838
1873-7560
DOI:10.1016/j.eururo.2012.09.007