Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Efficacy and safety of dutasteride, tamsulosin and their combination in a subpopulation of the CombAT study: 2-year results in Asian men with moderate-to-severe BPH

Prostate Cancer and Prostatic Diseases volume 12, pages 152–159 (2009)Cite this article

Abstract

Although ethnicity-based differences in prostate size and physiology have been reported, results of benign prostatic hyperplasia (BPH) treatment trials in predominantly Caucasian patients are assumed to be applicable to non-Caucasian populations. This post hoc analysis investigated whether an Asian subpopulation of men with moderate-to-severe BPH in the CombAT study achieves treatment responses in line with those of the overall study population. In this double-blind, randomized, parallel-group trial, 325 Asian men were assigned to treatment with 0.5 mg dutasteride once daily, 0.4 mg tamsulosin once daily or the combination. Decrease in international prostate symptom score (IPSS) at month 24 from baseline (the primary endpoint) was significantly greater with combination treatment compared with tamsulosin (P<0.05), and numerically, but not statistically significantly, greater compared with dutasteride. Mean IPSS was reduced from baseline by 7.5 (±0.84) in the combination group, by 6.3 (±0.86) in the dutasteride group and by 4.5 (±0.78) in the tamsulosin group, resulting in respective mean IPSS at months 24 of 11.4 (±0.60), 12.7 (±0.70) and 14.3 (±0.74). The adverse event profile was similar to that observed in the overall CombAT population, and drug-related adverse events were more common with combination therapy (26%) than with tamsulosin (15%) or dutasteride (9%). No unexpected adverse events emerged. In conclusion, in Asian men with moderate-to-severe lower urinary tract symptoms and an enlarged prostate, combination therapy achieved significantly greater improvements from baseline BPH symptoms, flow rate, quality of life, reduced prostate volume and improved treatment satisfaction compared with tamsulosin monotherapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. National Kidney and Urologic Diseases Information Clearing House (NKUDIC). Prostate enlargement: benign prostatic hyperplasia. [Cited 10 January 2008]; Available from: http://kidney.niddk.nih.gov/kudiseases/pubs/prostateenlargement/.

  2. Mariappan P, Turner KJ, Sothilingam S, Rajan P, Sundram M, Stewart LH . Nocturia, nocturia indices and variables from frequency–volume charts are significantly different in Asian and Caucasian men with lower urinary tract symptoms: a prospective comparison study. BJU Int 2007; 100: 332–336.

    Article  Google Scholar 

  3. Homma Y, Kawabe K, Tsukamoto T, Yamanaka H, Okada K, Okajima E et al. Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score. Int J Urol 1997; 4: 40–46.

    Article  CAS  Google Scholar 

  4. Kang D, Andriole GL, Van De Vooren RC, Crawford D, Chia D, Urban DA et al. Risk behaviours and benign prostatic hyperplasia. BJU Int 2004; 93: 1241–1245.

    Article  CAS  Google Scholar 

  5. Roehrborn C, McConnell JD . Etiology, pathophysiology, epidemiology and natural history of BPH. In: Walsh P (ed). Campbell's Urology. WB Saunders: Philadelphia, 2002, pp 1297–1336.

    Google Scholar 

  6. Oesterling JE, Kumamoto Y, Tsukamoto T, Girman CJ, Guess HA, Masumori N et al. Serum prostate-specific antigen in a community-based population of healthy Japanese men: lower values than for similarly aged white men. Br J Urol 1995; 75: 347–353.

    Article  CAS  Google Scholar 

  7. Lee SE, Kwak C, Park MS, Lee CH, Kang W, Oh SJ . Ethnic differences in the age-related distribution of serum prostate-specific antigen values: a study in a healthy Korean male population. Urology 2000; 56: 1007–1010.

    Article  CAS  Google Scholar 

  8. Masumori N, Tsukamoto T, Kumamoto Y, Miyake H, Rhodes T, Girman CJ et al. Japanese men have smaller prostate volumes but comparable urinary flow rates relative to American men: results of community based studies in 2 countries. J Urol 1996; 155: 1324–1327.

    Article  CAS  Google Scholar 

  9. Jin B, Turner L, Zhou Z, Zhou EL, Handelsman DJ . Ethnicity and migration as determinants of human prostate size. J Clin Endocrinol Metab 1999; 84: 3613–3619.

    CAS  PubMed  Google Scholar 

  10. Wang MZ, Gao ZW, He DL, Chen XF, He H, Wang WS et al. Age-specific reference ranges for serum prostate-specific antigen in Chinese men. Zhonghua Yi Xue Za Zhi 2003; 83: 1665–1667.

    PubMed  Google Scholar 

  11. Madanay LD, Johnson DB, Miyamoto LA, Gilbert Jr FI . Prostate-specific antigen concentration: influence of age and ethnicity. Hawaii Med J 1995; 54: 606–608.

    CAS  PubMed  Google Scholar 

  12. Cheng I, Yu MC, Koh WP, Pike MC, Kolonel LN, Henderson BE et al. Comparison of prostate-specific antigen and hormone levels among men in Singapore and the United States. Cancer Epidemiol Biomarkers Prev 2005; 14: 1692–1696.

    Article  CAS  Google Scholar 

  13. 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.

    Article  CAS  Google Scholar 

  14. Vela-Navarrete R, Gonzalez-Enguita C, Garcia-Cardoso JV, Manzarbeitia F, Sarasa-Corral JL, Granizo JJ . The impact of medical therapy on surgery for benign prostatic hyperplasia: a study comparing changes in a decade (1992–2002). BJU Int 2005; 96: 1045–1048.

    Article  Google Scholar 

  15. Boyle P, Roehrborn C, Harkaway R, Logie J, de la Rosette J, Emberton M . 5-Alpha reductase inhibition provides superior benefits to alpha blockade by preventing AUR and BPH-related surgery. Eur Urol 2004; 45: 620–626; [discussion 626–627].

    Article  CAS  Google Scholar 

  16. Barkin J, Guimaraes M, Jacobi G, Pushkar D, Taylor S, van Vierssen Trip OB . Alpha-blocker therapy can be withdrawn in the majority of men following initial combination therapy with the dual 5alpha-reductase inhibitor dutasteride. Eur Urol 2003; 44: 461–466.

    Article  CAS  Google Scholar 

  17. Marberger M, Harkaway R, de la Rosette J . Optimising the medical management of benign prostatic hyperplasia. Eur Urol 2004; 45: 411–419.

    Article  Google Scholar 

  18. Andriole G, Bruchovsky N, Chung LW, Matsumoto AM, Rittmaster R, Roehrborn C et al. Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia. J Urol 2004; 172: 1399–1403.

    Article  CAS  Google Scholar 

  19. Carson III C, Rittmaster R . The role of dihydrotestosterone in benign prostatic hyperplasia. Urology 2003; 61: 2–7.

    Article  Google Scholar 

  20. Gittelman M, Ramsdell J, Young J, McNicholas T . Dutasteride improves objective and subjective disease measures in men with benign prostatic hyperplasia and modest or severe prostate enlargement. J Urol 2006; 176: 1045–1050; [discussion 1050].

    Article  CAS  Google Scholar 

  21. Roehrborn CG . Combination medical therapy for lower urinary tract symptoms and benign prostatic hyperplasia. Rev Urol 2005; 7 (Suppl 8): S43–S51.

    PubMed  PubMed Central  Google Scholar 

  22. Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G . Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002; 60: 434–441.

    Article  Google Scholar 

  23. McConnell JD, Roehrborn CG, Bautista OM, Andriole Jr GL, Dixon CM, Kusek JW, et al., Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003; 349: 2387–2398.

    Article  CAS  Google Scholar 

  24. Roehrborn CG, Siami P, Barkin J, Damião R, Major-Walker K, Morrill B, et al., CombAT Study Group. The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. J Urol 2007; 179: 616–621.

    Article  Google Scholar 

  25. Siami P, Roehrborn CG, Barkin J, Damiao R, Wyczolkowski M, Duggan A, et al., CombAT study group. Combination therapy with dutasteride and tamsulosin in men with moderate-to-severe benign prostatic hyperplasia and prostate enlargement: the CombAT (Combination of Avodart and Tamsulosin) trial rationale and study design. Contemp Clin Trials 2007; 28: 770–779.

    Article  CAS  Google Scholar 

  26. Black L . The psychometric validation of a US English satisfaction measure in patients with benign prostatic hyperplasia. Abstract Presented at the 2008 International Society of Pharmacoeconomic and Outcomes Research (ISPOR), Toronto, Canada, May 2008.

  27. Lepor H . Long-term evaluation of tamsulosin in benign prostatic hyperplasia: placebo-controlled, double-blind extension of phase III trial. Tamsulosin Investigator Group. Urology 1998; 51: 901–906.

    Article  CAS  Google Scholar 

  28. Lepor H . Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia. Tamsulosin Investigator Group. Urology 1998; 51: 892–900.

    Article  CAS  Google Scholar 

  29. Narayan P, Lepor H . Long-term, open-label, phase III multicenter study of tamsulosin in benign prostatic hyperplasia. Urology 2001; 57: 466–470.

    Article  CAS  Google Scholar 

  30. Chung BH, Hong SJ, Lee MS . Doxazosin for benign prostatic hyperplasia: an open-label, baseline-controlled study in Korean general practice. Int J Urol 2005; 12: 159–165.

    Article  CAS  Google Scholar 

  31. Horiuchi K, Tsuboi N, Hattori T, Yoshida K, Akimoto M . The short-term effects of tamsulosin in Japanese men with benign prostatic hyperplasia. Nippon Ika Daigaku Zasshi 1999; 66: 382–387.

    Article  CAS  Google Scholar 

  32. Lee E . Comparison of tamsulosin and finasteride for lower urinary tract symptoms associated with benign prostatic hyperplasia in Korean patients. J Int Med Res 2002; 30: 584–590.

    Article  CAS  Google Scholar 

  33. Li NC, Chen S, Yang XH, Du LD, Wang JY, Na YQ . Efficacy of low-dose tamsulosin in chinese patients with symptomatic benign prostatic hyperplasia. Clin Drug Investig 2003; 23: 781–787.

    Article  CAS  Google Scholar 

  34. Park CH, Chang HS, Oh BR, Kim HJ, Sul CK, Chung SK et al. Efficacy of low-dose tamsulosin on lower urinary tract symptoms suggestive of benign prostatic hyperplasia: a nonblind multicentre korean study. Clin Drug Investig 2004; 24: 41–47.

    Article  CAS  Google Scholar 

  35. Suzuki H, Yano M, Awa Y, Nakatsu H, Egoshi K, Mikami K et al. Clinical impact of tamsulosin on generic and symptom-specific quality of life for benign prostatic hyperplasia patients: using international prostate symptom score and Rand Medical Outcomes Study 36-item Health Survey. Int J Urol 2006; 13: 1202–1206.

    Article  CAS  Google Scholar 

  36. Chueh SC, Yu HJ, Chiu TY, Huang CY, Lai MK . Treating benign prostatic hyperplasia with finasteride in Chinese men: one-year experience. J Formos Med Assoc 1996; 95: 650–652.

    CAS  PubMed  Google Scholar 

  37. Mochtar CA, Rahardjo D, Umbas R . A higher PSA-density cut-off level in patients with intermediate PSA values for the early detection of prostate cancer. Gan To Kagaku Ryoho 2000; 27 (Suppl 2): 514–522.

    PubMed  Google Scholar 

  38. Gupta A, Aragaki C, Gotoh M, Masumori N, Ohshima S, Tsukamoto T et al. Relationship between prostate specific antigen and indexes of prostate volume in Japanese men. J Urol 2005; 173: 503–506.

    Article  Google Scholar 

  39. Chang YL, Lin AT, Chen KK, Chang YH, Wu HH, Kuo JY et al. Correlation between serum prostate specific antigen and prostate volume in Taiwanese men with biopsy proven benign prostatic hyperplasia. J Urol 2006; 176: 196–199.

    Article  Google Scholar 

  40. Iehle C, Radvanyi F, Gil Diez de Medina S, Ouafik LH, Gérard H, Chopin D et al. Differences in steroid 5alpha-reductase iso-enzymes expression between normal and pathological human prostate tissue. J Steroid Biochem Mol Biol 1999; 68: 189–195.

    Article  CAS  Google Scholar 

  41. Boyle P, Gould AL, Roehrborn CG . Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology 1996; 48: 398–405.

    Article  CAS  Google Scholar 

  42. Lloyd SN, Kavanagh J, Chan PS, Ferreira AM, Gu FL, Pavone-Macaluso M et al. A multicentre prospective study of prostatic volume in asymptomatic men in various continents. Prostate Cancer Prostatic Dis 1997; 1: 97–100.

    Article  CAS  Google Scholar 

  43. McNeal JE . Origin and evolution of benign prostatic enlargement. Invest Urol 1978; 15: 340–345.

    CAS  PubMed  Google Scholar 

  44. Aoki Y, Arai Y, Maeda H, Okubo K, Shinohara K . Racial differences in cellular composition of benign prostatic hyperplasia. Prostate 2001; 49: 243–250.

    Article  CAS  Google Scholar 

  45. Schuster GA, Schuster TG . The relative amount of epithelium, muscle, connective tissue and lumen in prostatic hyperplasia as a function of the mass of tissue resected. J Urol 1999; 161: 1168–1173.

    Article  CAS  Google Scholar 

  46. Pettaway CA . Racial differences in the androgen/androgen receptor pathway in prostate cancer. J Natl Med Assoc 1999; 91: 653–660.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Zeigler-Johnson CM, Walker AH, Mancke B, Spangler E, Jalloh M, McBride S et al. Ethnic differences in the frequency of prostate cancer susceptibility alleles at SRD5A2 and CYP3A4. Hum Hered 2002; 54: 13–21.

    Article  CAS  Google Scholar 

  48. Chung BH, Hong SJ, Cho JS, Seong DH . Relationship between serum prostate-specific antigen and prostate volume in Korean men with benign prostatic hyperplasia: a multicentre study. BJU Int 2006; 97: 742–746.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Yonsei University Health System, Seoul, South Korea

    B-H Chung

  2. Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA

    C G Roehrborn

  3. Welborn Clinic, Evansville, IN, USA

    P Siami

  4. Clinical Development, GlaxoSmithKline, Research Triangle Park, NC, USA

    K Major-Walker

  5. Department of Biostatistics, GlaxoSmithKline, Research Triangle Park, NC, USA

    B B Morrill & T H Wilson

  6. Department of Urology, Universita Vita Salute San Raffaele, Milan, Italy

    F Montorsi

Authors
  1. B-H Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C G Roehrborn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P Siami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K Major-Walker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B B Morrill
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T H Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F Montorsi
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the CombAT Study Group

Corresponding author

Correspondence to B-H Chung.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chung, BH., Roehrborn, C., Siami, P. et al. Efficacy and safety of dutasteride, tamsulosin and their combination in a subpopulation of the CombAT study: 2-year results in Asian men with moderate-to-severe BPH. Prostate Cancer Prostatic Dis 12, 152–159 (2009). https://doi.org/10.1038/pcan.2008.49

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/pcan.2008.49

Keywords

This article is cited by

Search

Advanced search

Quick links