World Journal of Urology

, Volume 32, Issue 5, pp 1287–1294 | Cite as

Intermittent versus continuous cyproterone acetate in bone metastatic prostate cancer: results of a randomized trial

  • Paul C. M. S. VerhagenEmail author
  • Mark F. Wildhagen
  • Annet M. Verkerk
  • Egils Vjaters
  • Hembo Pagi
  • Leonhard Kukk
  • Dejan Bratus
  • Richard Fiala
  • Chris H. Bangma
  • Fritz H. Schröder
  • Gerald H. J. Mickisch
Original Article



To compare intermittent treatment (IT) versus continuous treatment (CT) using cyproterone acetate (CPA) in bone metastatic prostate cancer patients, we conducted an open-label, multicenter randomized trial. Continuous androgen deprivation therapy is the standard treatment in metastatic prostate cancer. Intermittent treatment might maintain efficacy while toxicity and costs are reduced.


Patients received CPA 100 mg tid in the prephase. Patients with a PSA decline of ≥90 % or PSA <4 ng/ml were randomized. If patients were progressive, LHRH analogues were added. Primary end point was time to PSA progression.


A total of 366 patients were recruited; 258 reached a good response after 3 or 6 months and were randomized. A total of 131 patients randomized to IT and 127 to CT. Patients on IT had an average of 1.7 episodes on CPA, before LHRH analogues were started. The mean time without treatment in IT was 463 days versus 422 days on treatment. There were statistical significant differences between IT and CT in 3 of the 5 functional scales of EORTC QLQ C 30; however, the clinical relevance of this finding appears modest. Symptom and potency scales showed significant advantages for IT. There were no differences in time to PSA progression on CPA, time to PSA and/or clinical progression on LHRH analogues and time to cancer-specific and overall survival.


IT by CPA is associated with less symptoms and modest advantages in QOL domains. There were no differences in time to PSA progression, clinical progression or survival.


Metastatic prostate cancer Androgen deprivation therapy (ADT) Intermittent ADT Cyproterone acetate (CPA) 



Bayer Pharma AG (former Schering AG) Berlin supported the trial. There was no role in the study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.

Conflict of interest

None of the authors has a conflict of interest.

Supplementary material

345_2013_1206_MOESM1_ESM.docx (69 kb)
Figure 4 Kaplan Meier curves showing results for continuous and intermittent treatment. a) time to overall progression in phase 1; b) cancer-specific survival; c) overall survival. (no significant differences). (DOCX 69 kb)


  1. 1.
    Conti PD, Atallah AN, Arruda H et al (2007) Intermittent versus continuous androgen suppression for prostatic cancer. Cochrane Database Syst Rev CD005009Google Scholar
  2. 2.
    Miller K, Steiner U, Lingnau A et al (2007) Randomised prospective study of intermittent versus continuous androgen suppression in advanced prostate cancer. J Clin Oncol 25: 2007 (suppl; abstr 5015)Google Scholar
  3. 3.
    Calais da Silva FE, Bono AV, Whelan P et al (2009) Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: results from a randomised phase 3 study of the South European uroncological group. Eur Urol 55:1269–1277PubMedCrossRefGoogle Scholar
  4. 4.
    Langenhuijsen JF, Badhauser D, Schaaf B et al (2011) Continuous versus intermittent androgen deprivation therapy for metastatic prostate cancer. Urol Oncol 31(5):549–556 Google Scholar
  5. 5.
    Hussain M, Tangen CM, Berry DL et al (2013) Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med 368:1314–1325PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Crook JM, O’Callaghan CJ, Duncan G et al (2012) Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med 367:895–903PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    de Leval J, Boca P, Yousef E et al (2002) Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone-naive prostate cancer: results of a prospective randomized multicenter trial. Clin Prostate Cancer 1:163–171PubMedCrossRefGoogle Scholar
  8. 8.
    Yamanaka H, Ito K, Naito S et al (2005) Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer. Prostate 63:56–64PubMedCrossRefGoogle Scholar
  9. 9.
    Salonen AJ, Taari K, Ala-Opas M et al (2012) The fin prostate study VII: intermittent versus continuous androgen deprivation in patients with advanced prostate cancer. J Urol 187:2074–2081PubMedCrossRefGoogle Scholar
  10. 10.
    Tunn UW, Canepa G, Kochanowsky A, Kienle E (2012) Testosterone recovery in the off-treatment time in prostate cancer patients undergoing intermittent androgen deprivation therapy. Prostate Cancer Prostatic Dis 15(3):296–302Google Scholar
  11. 11.
    Sternberg CN, Krainer M, Oh WK et al (2007) The medical management of prostate cancer: a multidisciplinary team approach. BJU Int 99:22–27PubMedCrossRefGoogle Scholar
  12. 12.
    Tyrrell CJ, Kaisary AV, Iversen P et al (1998) A randomised comparison of ‘Casodex’ (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol 33:447–456PubMedCrossRefGoogle Scholar
  13. 13.
    Thorpe SC, Azmatullah S, Fellows GJ, Gingell JC, O’Boyle PJ (1996) A prospective, randomised study to compare goserelin acetate (Zoladex) versus cyproterone acetate (Cyprostat) versus a combination of the two in the treatment of metastatic prostatic carcinoma. Eur Urol 29:47–54PubMedGoogle Scholar
  14. 14.
    Schroder FH, Collette L, de Reijke TM, Whelan P (2000) Prostate cancer treated by anti-androgens: is sexual function preserved? EORTC genitourinary group. European organization for research and treatment of cancer. Br J Cancer 82:283–290PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Verhagen PC, Wissenburg LD, Wildhagen MF et al (2008) Quality of life effects of intermittent and continuous hormonal therapy by cyproterone acetate (CPA) for metastatic prostate cancer. Eur Urol Suppl 7:206CrossRefGoogle Scholar
  16. 16.
    Communication: FDS (2010) Update to ongoing safety review of GnRH agonists and notification to manufacturers of GnRH agonists to add new safety information to labelling regarding increased risk of diabetes and certain cardiovascular diseases. US Food and Drug Administration Web siteGoogle Scholar
  17. 17.
    Nguyen PL, Je Y, Schutz FA et al (2011) Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA 306:2359–2366PubMedCrossRefGoogle Scholar
  18. 18.
    Bolla M, de Reijke TM, Van Tienhoven G et al (2009) Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 360:2516–2527PubMedCrossRefGoogle Scholar
  19. 19.
    Verhagen PC, Schroder FH, Collette L, Bangma CH (2010) Does local treatment of the prostate in advanced and/or lymph node metastatic disease improve efficacy of androgen-deprivation therapy? A systematic review. Eur Urol 58:261–269PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Paul C. M. S. Verhagen
    • 1
    Email author
  • Mark F. Wildhagen
    • 1
  • Annet M. Verkerk
    • 1
  • Egils Vjaters
    • 2
  • Hembo Pagi
    • 3
  • Leonhard Kukk
    • 3
  • Dejan Bratus
    • 4
  • Richard Fiala
    • 5
    • 6
  • Chris H. Bangma
    • 1
  • Fritz H. Schröder
    • 1
  • Gerald H. J. Mickisch
    • 7
  1. 1.Department of UrologyErasmus University Medical CenterRotterdamThe Netherlands
  2. 2.P. Stradins University HospitalRigaLatvia
  3. 3.North-Estonia Regional HospitalTallinnEstonia
  4. 4.General Hospital MariborMariborSlovenia
  5. 5.Urologicka klinika FNOlomoucCzech Republic
  6. 6.Department of UrologyColeraineUK
  7. 7.Centrum für Operative Urologie BremenBremenGermany

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