Intermittent androgen deprivation therapy for prostate cancer:a review of the recent literature and guidelines

Athanasios N. Argyropoulos, Iraklis Poulias


Androgen deprivation therapy is an established therapeutic option for prostate cancer patients, but is associated with serious side effects and quality of life issues. The purpose of this review is to present up - to - date results from randomized trials on intermittent androgen deprivation therapy and to identify those patients that will benefit the most from this approach.


Ο ανδρογονικός αποκλεισμός αποτελεί μια από πλέον καθιερωμένες θεραπευτικές επιλογές στον καρκίνο προστάτη, με σημαντικές ωστόσο ανεπιθύμητες ενέργειες και επίδραση στην ποιότητα ζωής. Σκοπός της ανασκόπησης είναι η παρουσίαση των σύγχρονων δεδομένων στο διακοπτόμενο αποκλεισμό με βάση πρόσφατες μελέτες και η αναζήτηση δεδομένων για την ομάδα ασθενών που θα ωφεληθεί περισσότερο από την προσέγγιση αυτή.



Androgen deprivation; intermittent; prostate cancer;Ανδρογονικός αποκλεισμός; διακοπτόμενος; καρκίνος προστάτη

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Boyle P, Ferlay J. Cancer incidence and mortality in Europe, 2004. Ann Oncol 2005, 16(3): 481 - 8

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin 2008, 58(2): 71 - 96

Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate.1941. J Urol 2002, 168(1): 9 - 12

Schally AV, Kastin AJ, Arimura A. Hypothalamic follicle-stimulating hormone (FSH) and luteinizing hormone(LH)-regulating hormone: structure, physiology, and clinical studies. Fertil Steril 1971, 22(11): 703 - 21

Klotz LH, Herr HW, Morse MJ, Whitmore WF Jr.Intermittent endocrine therapy for advanced prostate cancer. Cancer 1986, 58(11): 2546 - 50. Erratum in Cancer 1987, 59(10): 43

Bruchovsky N, Rennie PS, Coldman AJ, Goldenberg SL, To M, Lawson D. Effects of androgen withdrawal on the stem cell composition of the Shionogi carcinoma. Cancer Res 1990, 50(8): 2275 - 82

Akakura K, Bruchovsky N, Goldenberg SL, Rennie PS, Buckley AR, Sullivan LD. Effects of intermittent androgen suppression on androgen-dependent tumors.Apoptosis and serum prostate - specific antigen. Cancer 1993, 71(9): 2782 - 90

Zlotta A, Debruyne FMJ. Expert opinion on optimal testosterone control in prostate cancer. Eur Urol Suppl 2005, 4(8): 37 -41

Oefelein MG, Feng A, Scolieri MJ, Ricchiutti D, Resnick MI. Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making. Urology 2000, 56(6): 1021 - 4

Abrahamsson PA. Potential benefits of intermittent androgen suppression therapy in the treatment of prostate cancer: a systematic review of the literature. Eur Urol 2010, 57(1): 49 - 59

Bruchovsky N, Klotz L, Crook J, Malone S, Ludgate C, Morris WJ, et al. Final results of the Canadian prospective phase II trial of intermittent androgen suppression for men in biochemical recurrence after radiotherapy for locally advanced prostate cancer: clinical parameters. Cancer 2006, 107: 389 - 95

de La Taille A, Zerbib M, Conquy S, Amsellem - Ouazana D, Thiounn N, Flam TA, et al. Intermittent androgen suppression in patients with prostate cancer. BJU Int 2003, 91: 18 - 22

Pether M, Goldenberg SL, Bhagirath K, Gleave M Intermittent androgen suppression in prostate cancer: an update of the Vancouver experience. Can J Urol 2003, 10: 1809 - 14

Prapotnich D, Fizazi K, Escudier B,Mombet A, Cathala N, Vallancien G. A 10-year clinical experience with intermittent hormonal therapy for prostate cancer. Eur Urol 2003, 43: 233 - 40, discussion 239 - 40

Spry NA, Kristjanson L, Hooton B, Hayden L, Neerhut G, Gurney H, et al. Adverse effects to quality of life arising from treatment can recover with intermittent androgen suppression in men with prostate cancer. Eur J Cancer 2006, 42: 1083 - 92

Grossfeld GD, Small EJ, Carroll PR.Intermittent androgen deprivation for clinically localized prostate cancer: initial experience. Urology 1998, 51: 137 - 44

Malone S, Perry G, Eapen L, Segal R, Gallant V, Dahrouge S, Crook J, et al. Mature results of the Ottawa phase II study of intermittent androgen-suppression therapy in prostate cancer: clinical predictors of outcome. Int J Radiat Oncol Biol Phys 2007, 68: 699 - 706

Youssef E, Tekyi-Mensah S, Hart K, Bolton S, Forman J. Intermittent androgen deprivation for patients with recurrent/metastatic prostate cancer. Am J Clin Oncol 2003, 26: 119 - 23

Shaw GL, Wilson P, Cuzick J, Prowse DM, Goldenberg SL, Spry NA, et al. International study into the use of intermittent hormone therapy in the treatment of carcinoma of the prostate: a meta - analysis of 1446 patients. BJU Int 2007, 99(5): 1056 - 65

Bouchot O, Lenormand L, Karam G, Prunet D, Gaschignard N, Malinovsky JM, et al. Intermittent androgen suppression in the treatment of metastatic prostate cancer. Eur Urol 2000, 38(5): 543 - 9

Sato N, Akakura K, Isaka S, Nakatsu H, Tanaka M, Ito H, et al. Intermittent androgen suppression for locally advanced and metastatic prostate cancer: preliminary report of a prospective multicenter study. Urology 2004, 64(2): 341 - 5

Klotz L, Toren P. Androgen deprivation therapy in advanced prostate cancer: is intermittent therapy the new standard of care? Curr Oncol 2012, 19(Suppl 3): S13 - 21

Sciarra A, Abrahamsson PA, Brausi M, Galsky M, Mottet N, Sartor O, et al. Intermittent androgen - deprivation therapy in prostate cancer: a critical review focused on phase 3 trials. Eur Urol 2013, 64(5): 722 - 30

Calais da Silva FE, Bono AV, Whelan P, Brausi M, Marques Queimadelos A, Martin JA, et al. 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 2009, 55(6): 1269 - 77

Salonen AJ, Taari K, Ala - Opas M, Viitanen J, Lundstedt S, Tammela TL. Advanced prostate cancer treated with intermittent or continuous androgen deprivation in the randomised FinnProstate Study VII: quality of life and adverse effects. Eur Urol 2013, 63(1): 111 - 20

Mottet N, Van Damme J, Loulidi S, Russel C, Leitenberger A, Wolff JM.Intermittent hormonal therapy in the treatment of metastatic prostate cancer: a randomized trial. BJU Int 2012, 110(9): 1262 - 9

Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, et al. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med 2013, 368(14): 1314 - 25

Crook JM, O’Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, et al. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med 2012, 367(10): 895 - 903

Calais da Silva F, Calais da Silva FM, Goncalves F, Santos A, Kliment J, Whelan P, et al. Locally advanced and metastatic prostate cancer treated with intermittent androgen monotherapy or maximal androgen blockade: Results from a randomised phase 3 study by the South European Uroncological Group. Eur Urol 2013. 055

Piaggio G, Elbourne DR, Altman DG, Pocock SJ, Evans SJ; CONSORT Group. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA 2006, 295(10): 1152 - 60

Moinpour CM, Hayden KA, Thompson IM, Feigl P, Metch B. Quality of life assessment in Southwest Oncology Group trials. Oncology (Williston Park) 1990, 4(5): 79 - 84

Verhagen PCMS, Wissenburg LD, Wildhagen MF, Bolle WABM, Verkerk AM, Schroder FH, et al. Quality of life effects of intermittent and continuous hormonal therapy by cyproterone acetate (CPA) for metastatic prostate cancer [abstract 541] Eur Urol Suppl 2008, 7: 206

Gruca D, Bacher P and Tunn U. Safety and tolerability of intermittent androgen deprivation therapy: A literature review. Int J Urol 2012, 19: 624 - 5

de Leval J, Boca P, Yousef E, Nicolas H, Jeukenne M, Seidel L, et al. Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone-naïve prostate cancer: results of a prospective randomized multicenter trial. Clin Prostate Cancer 2002, 1: 163 - 71

Gleave M, Klotz I, Taneja SS. The continued debate: intermittent vs. continuous hormonal ablation for metastatic prostate cancer. Urol Oncol 2009, 27: 81 - 6

Keizman D, Huang P, Antonarakis ES, Sinibaldi V, Carducci MA, Denmeade S, et al. The change of PSA doubling time and its association with disease progression in patients with biochemically relapsed prostate cancer treated with intermittent androgen deprivation. Prostate 2011, 71: 1608 - 15

Sciarra A, Cattarino S, Gentilucci A, et al. Predictors for response to intermittent androgen deprivation in prostate cancer patients with biochemical progression after surgery. Urol Oncol 2013, 31(5): 607 - 14

Yu YJ, Gulati R, Telesca D, Jiang P, Tam S, Russell KJ, et al. Duration of first off-treatment interval is prognostic for time to castration resistance and death in men with biochemical relapse of prostate cancer treated on a prospective trial of intermittent androgen deprivation. J Clin Oncol 2010, 28: 2668 - 73

Langenhuijsen JF, Badhauser D, Schaaf B, Kiemeney LA, Witjes JA, Mulders PF. Continuous vs. intermittent androgen deprivation therapy for metastatic prostate cancer. Urol Oncol 2013, 31(5): 549 - 56

Benaim EA, Pace CM, Lam PM, Roehrborn CG. Nadir prostate - specific antigen as a predictor of progression to androgen - independent prostate cancer. Urology 2002, 59: 73 - 8

Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, Mason MD, et al. Guidelines on prostate cancer. European Association of Urology Web site.

Prostate cancer. Guidelines for the management of clinically localized prostate cancer: 2007 update. American Urological Association Web site. prostate-cancer.cfm

Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben - Josef E, Mendelson DS, et al. American Society of Clinical Oncology. Initial hormonal management of androgen - sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol 2007, 25: 1596 - 605

Mohler JL, Kantoff PW, Armstrong AJ, Bahnson RR, Cohen M, D’Amico AV, et al. Prostate cancer, version 1.2014. J Natl Compr Canc Netw 2013, 11: 1471 - 9