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:

Bicalutamide 80 mg combined with a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A monotherapy in advanced prostate cancer: findings from a phase III randomized, double-blind, multicenter trial in Japanese patients

Prostate Cancer and Prostatic Diseases volume 10, pages 194–201 (2007)Cite this article

Abstract

To compare combination therapy with bicalutamide 80 mg and a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A alone in Japanese men with untreated advanced prostate cancer. A total of 205 patients with stage C/D prostate cancer were randomized to either LHRH-A+once-daily oral bicalutamide 80 mg or placebo. Primary study variables have been reported previously. Secondary variables included: time to achieve prostate-specific antigen⩽4 ng/ml, time-to-treatment failure (TTTF), time-to-disease progression (TTP), overall survival (OS), adverse events and adverse drug reactions. Following combination therapy with bicalutamide 80 mg, there were significant (P<0.001) advantages over LHRH-A alone in terms of TTTF and TTP, but the difference in the interim OS was not statistically significant. First-line combination therapy with bicalutamide 80 mg in Japanese patients with advanced prostate cancer offers significant benefits over LHRH-A alone, with respect to TTTF and TTP. Follow-up for OS continues.

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
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Cancer Registration Committee of the Japanese Urological Association. Clinicopathological statistics on registered prostate cancer patients in Japan: 2000 report from the Japanese Urological Association. Int J Urol 2005; 12: 46–61.

  2. Akaza H, Usami M, Hinotsu S, Ogawa O, Kagawa S, Kitamura T et al. Characteristics of patients with prostate cancer who have initially been treated by hormone therapy in Japan: J-CaP surveillance. Jpn J Clin Oncol 2004; 34: 329–336.

    Article  Google Scholar 

  3. Klotz L, Schellhammer P, Carroll K . A re-assessment of the role of combined androgen blockade for advanced prostate cancer. BJU Int 2004; 93: 1177–1182.

    Article  CAS  Google Scholar 

  4. Prostate Cancer Trialists' Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet 2000; 355: 1491–1498.

  5. Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL et al. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group. Urology 1997; 50: 330–336.

    Article  CAS  Google Scholar 

  6. Akaza H, Homma Y, Okada K, Yokoyama M, Usami M, Hirao Y et al. A prospective and randomized study of primary hormonal therapy for patients with localized or locally advanced prostate cancer unsuitable for radical prostatectomy: results of the 5-year follow-up. BJU Int 2003; 91: 33–36.

    Article  CAS  Google Scholar 

  7. Kotake T, Usami M, Akaza H, Koiso K, Homma Y, Kawabe K et al. Goserelin acetate with or without antiandrogen or estrogen in the treatment of patients with advanced prostate cancer: a multicenter, randomized, controlled trial in Japan. Zoladex Study Group. Jpn J Clin Oncol 1999; 29: 562–570.

    Article  CAS  Google Scholar 

  8. Kanetake H, Akaza H, Usami M . A phase III randomized trial of low dose flutamide compared with luteinizing hormone releasing agonist (LHRHa) vs LHRHa monotherapy for advanced prostate cancer. Japan Flutamide Study Cooperative Group. BJU Int 2004; 94: 58–59 (abstract).

    Google Scholar 

  9. Akaza H, Yamaguchi A, Matsuda T, Igawa M, Kumon H, Soeda A et al. Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients. Jpn J Clin Oncol 2004; 34: 20–28.

    Article  Google Scholar 

  10. Kotake T, Akaza H, Usami M, Isaka S, Homma Y, Oishi K et al. Preliminary trial for clinical phase III study of Casodex (Bicalutamide ICI 176,334). J New Remedies Clinics 1999; 48: 1512–1533.

    Google Scholar 

  11. Kotake T, Usami M, Isaka S, Shimazaki J, Oishi K, Yoshida O et al. Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer. Hinyokika Kiyo 1996; 42: 143–153.

    CAS  PubMed  Google Scholar 

  12. Kotake T, Usami M, Isaka S, Shimazaki J, Nakano E, Okuyama A et al. Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer. Hinyokika Kiyo 1996; 42: 157–168.

    CAS  PubMed  Google Scholar 

  13. Japanese Urological Association and The Japanese Pathological Society. General Rule for Clinical and Pathological Studies on Prostate Cancer. Kanehara: Tokyo, Japan, 1992, pp 100–106.

  14. Small EJ, Carroll PR . Prostate-specific antigen decline after casodex withdrawal: evidence for an antiandrogen withdrawal syndrome. Urology 1994; 43: 408–410.

    Article  CAS  Google Scholar 

  15. Nieh PT . Withdrawal phenomenon with the antiandrogen casodex. J Urol 1995; 153: 1070–1073.

    Article  CAS  Google Scholar 

  16. Schellhammer PF, Venner P, Haas GP, Small EJ, Nieh PT, Seabaugh DR et al. Prostate specific antigen decreases after withdrawal of antiandrogen therapy with bicalutamide or flutamide in patients receiving combined androgen blockade. J Urol 1997; 157: 1731–1735.

    Article  CAS  Google Scholar 

  17. Aus G, Abbou CC, Bolla M, Heidenreich A, Schmid HP, van Poppel H et al. European Association of Urology Guidelines on Prostate Cancer 2005, (online). http://www.uroweb.nl/files/uploaded_files/2005ProstateCancer.pdf.

  18. Kojima S, Suzuki H, Akakura K, Shimbo M, Ichikawa T, Ito H . Alternative antiandrogens to treat prostate cancer relapse after initial hormone therapy. J Urol 2004; 171: 679–683.

    Article  CAS  Google Scholar 

  19. Kaisary AV . Compliance with hormonal treatment for prostate cancer. Br J Hosp Med 1996; 55: 359–366.

    CAS  PubMed  Google Scholar 

  20. Fourcade R-O, McLeod D . Tolerability of antiandrogens in the treatment of prostate cancer. Uro Oncol 2004; 4: 5–13.

    CAS  Google Scholar 

Download references

Acknowledgements

Financial sponsorship for this trial was provided by AstraZeneca.

We thank Dr Chris Rapier, PhD, from Complete Medical Group, who provided editing assistance on behalf of AstraZeneca. We also thank Dr Toshihiko Kotake for valuable medical advice and the study institutions for data collection.

Study institutions, listed in descending order of the number of patients that they enlisted*, were:

Harasanshin Hospital (22); Kansai Medical University Hospital (nine); Shimane University Hospital (eight); Nishi-Kobe Medical Center (seven); Okayama University Hospital (seven); Fujieda Municipal General Hospital (six); Kurashiki Central Hospital (six); Nihon University Itabashi Hospital (six); Shikoku Cancer Center (six); Showa University Hospital (six); Tokushima University Hospital (six); Gifu University Hospital (five); Kanazawa University Hospital (five); Kobe University Hospital (five); Kyushu University Hospital (five); Nagasaki Medical Center (five); Nara University of Medical Science Hospital (five); Tokyo Medical University Hospital (five); Hirosaki University School of Medicine and Hospital (four); Hiroshima University Hospital (four); Kawasaki Medical School Hospital (four); Keio University Hospital (four); Kyoto University Hospital (four); Nagasaki University Hospital (four); Osaka University Hospital (four); Sasebo Municipal General Hospital (four); Tokyo Women's Medical University Hospital (four); Kitasato University Hospital (three); Osaka City University Hospital (three); The University of Tokyo Hospital (three); Teikyo University Ichihara Hospital (three); University Hospital, Kyoto Prefectural University of Medicine (three); Yamagata University Hospital (three); Asahi Central Hospital (two); Jikei University School of Medicine Hospital (two); Kochi Medical School Hospital (two); Nagoya City University Hospital (two); Nagoya Daini Red Cross Hospital (two); Niigata Cancer Center Hospital (two); Niigata University Medical and Dental Hospital (two); Sapporo Medical University Hospital (two); Tohoku University Hospital (two); Tsukuba University Hospital (two); Yokohama City University Hospital (two); Chiba University Hospital (one); Hokkaido University Hospital (one); Osaka Medical Center for Cancer and Cardiovascular Diseases (one); Toranomon Hospital (one); Tottori University Hospital (one).

*Values in parentheses represent the number of enrolled patients.

Author information

Authors and Affiliations

  1. Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    M Usami

  2. Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan

    H Akaza

  3. Department of Urology, Tohoku University School of Medicine, Miyagi, Japan

    Y Arai

  4. Department of Urology, Fujieda Municipal General Hospital, Shizuoka, Japan

    Y Hirano

  5. Department of Urology, Tokushima University Hospital, Tokushima, Japan

    S Kagawa

  6. Department of Urology, Nagasaki University School of Medicine, Nagasaki, Japan

    H Kanetake

  7. Department of Urology, Kyushu University Hospital, Fukuoka, Japan

    S Naito

  8. Shikoku Cancer Center, Ehime, Japan

    Y Sumiyoshi

  9. Department of Urology, Nihon University Itabashi Hospital, Tokyo, Japan

    Y Takimoto

  10. Department of Urology, Kurashiki Central Hospital, Okayama, Japan

    A Terai

  11. Showa University Hospital, Tokyo, Japan

    H Yoshida

  12. Department of Biostatistics, School of Health Sciences and Nursing, The University of Tokyo, Tokyo, Japan

    Y Ohashi

Authors
  1. M Usami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H Akaza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y Arai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y Hirano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Kagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H Kanetake
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Naito
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y Sumiyoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Y Takimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A Terai
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. H Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Y Ohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Usami.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Usami, M., Akaza, H., Arai, Y. et al. Bicalutamide 80 mg combined with a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A monotherapy in advanced prostate cancer: findings from a phase III randomized, double-blind, multicenter trial in Japanese patients. Prostate Cancer Prostatic Dis 10, 194–201 (2007). https://doi.org/10.1038/sj.pcan.4500934

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.pcan.4500934

Keywords

This article is cited by

Search

Advanced search

Quick links