GSK?s Avodart / tamsulosin combination showed benefits for men with prostate enlargement
MISSISSAUGA, ON (October 13, 2009) The final results from a large, 4-year study showed that Avodart (dutasteride) and tamsulosin combination treatment reduced the risk of acute urinary retention (AUR) or Benign Prostatic Hyperplasia* (BPH)-related surgery and reduced the risk of BPH clinical progression more than tamsulosin alone**. Combination treatment also provided statistically greater improvements in symptom scores which were sustained from month nine compared to either dutasteride or tamsulosin monotherapy.
“For many men BPH is a progressive disease causing discomfort, inconvenience and embarrassment. CombAT provides evidence that dutasteride and tamsulosin together may benefit these men, potentially reducing the long-term risk of disease progression and improving their symptoms.” said Dr Claus G. Roehrborn, principal investigator and lead author of the CombAT study publication.
The GSK-sponsored Combination therapy with Avodart and tamsulosin (CombAT) study, (just published online in European Urology)1, showed a significant 66 percent reduction in the risk of AUR or BPH-related surgery with combination treatment compared to tamsulosin (p < 0.001). There was a 20 percent reduction compared to dutasteride (p= 0.18).
The risk of BPH clinical progression with combination treatment was reduced by 44 percent compared to tamsulosin and 31 percent for those on dutasteride. Men in this study who had moderate-to-severe symptoms of BPH at enrolment, reported a significant improvement in BPH symptoms at 4 years, with a mean change from baseline of -6.3 points, compared to -3.8 for tamsulosin and -5.3 for dutasteride alone, as measured by the International Prostate Symptom Score (IPSS)***.
“Benign Prostatic Hyperplasia affects more than 50 per cent of men over the age of 50, and is a disease that significantly affects quality of life. If not treated, the real concern and fear for most men is the fact that it will progress, leading to increased symptoms, urinary retention and possibly the need for a catheter or surgery,” says Dr. Jack Barkin, urologic surgeon and Chief of Staff, Humber River Regional Hospital, Toronto, and co-author of the study. “The good news for men with BPH is that the CombAT study has further reinforced the improvement in symptoms for men treated with tamsulosin and dutasteride combination therapy compared to either monotherapy, and that the improvement continues year upon year.”
The combination therapy was generally well-tolerated and most reported drug-related adverse events were as anticipated from the known safety profiles of the two drugs, with erectile dysfunction and retrograde ejaculation as the most commonly reported drug-related adverse events. However, the incidence of heart failure observed was higher in the combination (0.9%) and tamsulosin arms (0.6%) than in the dutasteride group (0.2%). There was no difference in overall cardiovascular events across treatment groups.
Treating men with symptomatic enlarged prostate is important because if left untreated, in some men BPH can lead to AUR, a complete obstruction of urinary excretion, and BPH-related surgery.2 Affecting nearly 50% of men over 50 years old,3,4 BPH is not life threatening, but its symptoms such as, hesitancy, interrupted weak urine flow, leaking or dribbling and more frequent urges and urination, may negatively affect patients suffering from BPH.5
* BPH is also known as Enlarged Prostate (EP).
** Tamsulosin is not indicated to reduce the risk of AUR or BPH-related surgery.
*** IPSS is a validated 7-item self-reported questionnaire designed to quantify urinary symptoms.
About CombAT
• CombAT was a 4-year multinational randomised study of 4,844 men at increased risk of BPH progression, investigating whether combination treatment with the 5-alpha reductase inhibitor (5ARI), dutasteride (0.5mg), and an alpha blocker, tamsulosin (0.4mg), was more effective than either monotherapy in improving symptoms and clinical outcome in men with moderate-to-severe symptomatic BPH.
• In Canada there were 32 sites and 347 randomized patients
• The primary end-point at 4 years was time to first AUR event or BPH-related surgery. Secondary end-points included clinical progression of BPH (defined as one of the following: symptom deterioration by IPSS ≥4 points on two consecutive visits; BPH-related AUR; BPH-related urinary incontinence; recurrent BPH-related Urinary Tract Infections (UTI) or urosepsis; BPH-related renal insufficiency), symptom improvement, urinary flow rate improvements, prostate volume and serum Prostate Specific Antigen (PSA) changes.
About dutasteride
Dutasteride is a dual inhibitor of type 1 and type 2 forms of the enzyme 5-alpha reductase which converts testosterone into dihydrotestosterone (DHT), the primary male hormone responsible for prostate growth and BPH development.6
Avodart is indicated for the treatment of symptomatic Benign Prostatic Hyperplasia (BPH) in men with enlarged prostates. The safety and efficacy of Avodart in combination with the alpha blocker tamsulosin is still under investigation and market authorization in Canada has not yet been obtained,
Women and children should not take dutasteride. Women who are or could become pregnant should not handle dutasteride due to the potential risk of a specific birth defect. Blood should not be donated until at least 6 months following the last dose of dutasteride. Possible side effects include sexually related side effects and swelling or tenderness of the breast. Other urological diseases, including prostate cancer, should be ruled out prior to treatment with dutasteride.
GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and health-care companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. In Canada, GlaxoSmithKline is among the top 15 investors in research and development, contributing more than $176 million in 2006 alone. GSK is an Imagine Caring Company, and is consistently recognized as one of the 50 Best Employers in Canada. For company information, please visit www.gsk.ca.
References
1. Roehrborn CG, Siami P, Barkin J, Damia R, Major-Walker K, The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Outcomes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results from the CombAT Study, Eur Urol (2009), doi:10.1016/j.eururo.2009.09.035
2. Indrani Nandy e, Betsy B. Morrill e, R. Paul Gagnier e, Francesco Montorsi
3. Marberger M, Harkaway R and de la Rosette J. Optimising the Medical Management of Benign Prostatic Hyperplasia. European Urology 45 (2004) 411–419
4. Napalkov P, Maisonneuve P, Boyle P. Worldwide patterns of prevalence and mortality from benign prostatic hyperplasia. Urology 1995; 46: 41-46
5. McVary KT. BPH: Epidemiology and Comorbidities. Am J of Managed Care 2006; 12 (5): 122-128
6. Levy A, Samraj GP. Benign prostatic hyperplasia: when to 'watch and wait,' when and how to treat. Cleve Clin J Med. 2007;74 Suppl 3:S15-20
7. Clark RV, Hermann DJ, Cunningham GR, Wilson TH, Morrill BB, Hobbs S. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab 2004; 89: 2179-2184
8. GSK. Avodart Summary of Product Characteristics. GSK UK, Uxbridge, Middlesex; 2008. http://emc.medicines.org.uk/medicine/11618
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Posted: October 2009
