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Antiandrogen treatments in locally advanced prostate cancer: are they all the same?

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Abstract

Purpose

The objectives are to review the published literature and to evaluate the weight of evidence for clinical effectiveness, safety, and tolerability of the currently available antiandrogens in the treatment of locally advanced prostate cancer. This article covers efficacy as monotherapy relative to castration and as adjuvant to radiotherapy and radical prostatectomy as well as adverse-effect and quality-of-life data.

Methods

The current literature from online databases between 1986 and the present, relating to antiandrogen treatments in men with locally advanced disease given either as monotherapy or as adjuvant to radical radiotherapy or prostatectomy, was reviewed. Antiandrogens researched included the non-steroidal antiandrogens, bicalutamide (‘Casodex’), flutamide, and nilutamide, and the steroidal antiandrogen cyproterone acetate (CPA).

Results

The most comprehensively investigated and reported antiandrogen is bicalutamide, which has shown survival outcomes similar to those observed with castration in patients with locally advanced prostate cancer. In contrast, only limited clinical data are available for the other non-steroidal antiandrogens (flutamide and nilutamide) and the steroidal antiandrogen CPA in patients with locally advanced disease. In terms of safety and tolerability, CPA is associated with loss of libido and erectile dysfunction. CPA is also associated with cardiovascular risk and there have been occasional reports of fatal fulminant hepatitis and hepatocellular carcinoma. Gynecomastia is quite rare with CPA, which is in contrast to the non-steroidal antiandrogens. There are no direct comparisons between the three non-steroidal antiandrogens in terms of quality of life, but available evidence suggests that bicalutamide has a more favorable safety and tolerability profile than nilutamide and flutamide. Unlike CPA, non-steroidal antiandrogens appear to be better tolerated than castration, allowing patients to maintain sexual activity, physical ability, and bone mineral density, but these agents have a higher incidence of gynecomastia and breast pain (mild to moderate in > 90% of cases). Gynecomastia and breast pain, however, can be effectively managed.

Conclusions

The available evidence indicates that the different antiandrogens should not be regarded as equivalents in clinical practice and so the choice of treatment for patients with prostate cancer should be made on an individual basis. It is, therefore, important for clinicians to discuss the efficacy and tolerability profiles of all available treatment options with their patients to enable them to choose a treatment program that best fits with their lifestyle.

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References

  • Adelson KB, Loprinzi CL, Hershman DL (2005) Treatment of hot flushes in breast and prostate cancer. Expert Opin Pharmacother 6:1095–1106

    Article  PubMed  CAS  Google Scholar 

  • Anderson J (2003) The role of antiandrogen monotherapy in the treatment of prostate cancer. BJU Int 91:455–461

    Article  PubMed  CAS  Google Scholar 

  • Aus G, Abbou CC, Bolla M, Heidenreich A, Van Poppel H, Schmid H-P, Wolff JM, Zattoni F (2005) European Association of Urology guidelines on prostate cancer. http://www.uroweb.nl/files/uploaded_files/2005Prostate%20Cancer.pdf (accessed 19 December 2005)

  • Barradell LB, Faulds D (1994) Cyproterone. A review of its pharmacology and therapeutic efficacy in prostate cancer. Drugs Aging 5:59–80

    Article  PubMed  CAS  Google Scholar 

  • Berruti A, Dogliotti L, Terrone C, Cerruti S, Isaia G, Tarabuzzi R, Reimondo G, Mari M, Ardissone P, De Luca S, Fasolis G, Fontana D, Rossetti SR, Angeli A, Gruppo Onco Urologico Piemontese (GOUP) ROP (2002) Changes in bone mineral density, lean body mass and fat content as measured by dual energy x-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation. J Urol 167:2361–2367

    Google Scholar 

  • Bill-Axelson A, Holmberg L, Ruutu M, Haggman M, Andersson SO, Bratell S, Spangberg A, Busch C, Nordling S, Garmo H, Palmgren J, Adami HO, Norlen BJ, Johansson JE (2005) Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 352:1977–1984

    Article  PubMed  CAS  Google Scholar 

  • Boccardo F, Rubagotti A, Barichello M, Battaglia M, Carmignani G, Comeri G, Conti G, Cruciani G, Dammino S, Delliponti U, Ditonno P, Ferraris V, Lilliu S, Montefiore F, Portoghese F, Spano G, for the Italian Prostate Cancer Project (1999) Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer patients: results of an Italian Prostate Cancer Project study. J Clin Oncol 17:2027–2038

    Google Scholar 

  • Boccardo F, Rubagotti A, Battaglia M, Di Tonno P, Selvaggi FP, Conti G, Comeri G, Bertaccini A, Martorana G, Galassi P, Zattoni F, Macchiarella A, Siragusa A, Muscas G, Durand F, Potenzoni D, Manganelli A, Ferraris V, Montefiore F (2005) Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer. J Clin Oncol 23:808–815

    Article  PubMed  CAS  Google Scholar 

  • Boccon-Gibod L, Fournier G, Bottet P, Marechal JM, Guiter J, Rischman P, Hubert J, Soret JY, Mangin P, Mallo C, Esctein Fraysse C (1997) Flutamide versus orchidectomy in the treatment of metastatic prostate carcinoma. Eur Urol 32:391–396

    PubMed  CAS  Google Scholar 

  • Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff R-O, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Cutajar CL, Zurlo A, Pierart M (2002) Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 360:103–108

    Article  PubMed  CAS  Google Scholar 

  • Boyle P, Ferlay J (2005) Cancer incidence and mortality in Europe, 2004. Ann Oncol 16:481–488

    Article  PubMed  CAS  Google Scholar 

  • Chang A, Yeap B, Davis T, Blum R, Hahn R, Khanna O, Fisher H, Rosenthal J, Witte R, Schinella R, Trump D (1996) Double-blind, randomized study of primary hormonal treatment of stage D2 prostate carcinoma: flutamide versus diethylstilbestrol. J Clin Oncol 14:2250–2257

    PubMed  CAS  Google Scholar 

  • Conti G, Cretarola E, Boccardo F, Battaglia M, Di Tonno P, De Antoni P, Zattoni F, Galassi P, Durand F (2004) Tamoxifen is safe and effective in preventing gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer and does not alter treatment efficacy (abs 221). Eur Urol Suppl 3:58

    Article  Google Scholar 

  • Daniell HW, Dunn SR, Ferguson DW, Lomas G, Niazi Z, Stratte PT (2000) Progressive osteoporosis during androgen deprivation therapy for prostate cancer. J Urol 163:181–186

    Article  PubMed  CAS  Google Scholar 

  • Debruyne FJM, Murray R, Fradet Y, Johansson JE, Tyrrell C, Boccardo F, Denis L, Marberger JM, Brune D, Rassweiler J, Vangeneugden T, Bruynseels J, Janssens M, De Porre P, for the Liarozole Study Group (1998) Liarozole—a novel treatment approach for advanced prostate cancer: results of a large randomized trial versus cyproterone acetate. Urology 52:72–81

    Google Scholar 

  • Decensi AU, Boccardo F, Guarneri D, Positano N, Paoletti MC, Costantini M, Martorana G, Giuliani L, for the Italian Prostatic Cancer Project (1991) Monotherapy with nilutamide, a pure nonsteroidal antiandrogen, in untreated patients with metastatic carcinoma of the prostate. J Urol 146:377–381

    Google Scholar 

  • Dole EJ, Holdsworth MT (1997) Nilutamide: an antiandrogen for the treatment of prostate cancer. Ann Pharmacother 31:65–75

    PubMed  CAS  Google Scholar 

  • Fourcade R-O, McLeod D (2004) Tolerability of antiandrogens in the treatment of prostate cancer. UroOncology 4:5–13

    Article  CAS  Google Scholar 

  • Gillatt DA, Bolton CH, Chadwick D, Downs LG, Hopton MI, Gingell JC (1993) Lipoprotein levels following treatment with cyproterone acetate or LHRH analogues. Br J Urol 71:728–730

    PubMed  CAS  Google Scholar 

  • Higano CS (2003) Side effects of androgen deprivation therapy: monitoring and minimizing toxicity. Urology 61:32–38

    Article  PubMed  Google Scholar 

  • Hull GW, Rabbani F, Abbas F, Wheeler TM, Kattan MW, Scardino PT (2002) Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urol 167:528–534

    Article  PubMed  Google Scholar 

  • Isurugi K, Fukutani K, Ishida H, Hosoi Y (1980) Endocrine effects of cyproterone acetate in patients with prostatic cancer. J Urol 123:180–183

    PubMed  CAS  Google Scholar 

  • Iversen P, Melezinek I, Schmidt A (2001) Nonsteroidal antiandrogens: a therapeutic option for patients with advanced prostate cancer who wish to retain sexual interest and function. BJU Int 87:47–56

    Article  PubMed  CAS  Google Scholar 

  • Iversen P, Tyrrell CJ, Kaisary AV, Anderson JB, Van Poppel H, Tammela TL, Chamberlain M, Carroll K, Melezinek I (2000) Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup. J Urol 164:1579–1582

    Article  PubMed  CAS  Google Scholar 

  • Iversen P, Tammela TLJ, Vaage S, Lukkarinen O, Lodding P, Bull-Njaa T, Viitanen J, Hoisaeter P, Lundmo P, Rasmussen F, Johansson J-E, Persson B-E, Carroll K, Scandinavian Prostatic Cancer Group (SPCG) (2002) A randomised comparison of bicalutamide (‘Casodex’) 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group study no. 6. Eur Urol 42:204–211

    Google Scholar 

  • Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R (1980) Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial. Br J Urol 52:208–215

    PubMed  CAS  Google Scholar 

  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics, 2006. CA Cancer J Clin 56:106–130

    PubMed  Google Scholar 

  • Kirby R (1998) Treatment options for early prostate cancer. Urology 52:948–962

    Article  PubMed  CAS  Google Scholar 

  • Lund F, Rasmussen F (1988) Flutamide versus stilboestrol in the management of advanced prostatic cancer. A controlled prospective study. Br J Urol 61:140–142

    Article  PubMed  CAS  Google Scholar 

  • McLeod DG, Iversen P, See WA, Morris T, Armstrong J, Wirth MP, on behalf of the ‘Casodex’ Early Prostate Cancer Trialists’ Group (2006) Bicalutamide 150 mg plus standard care versus standard care alone for early prostate cancer. BJU Int 97:247–254

  • Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D (1999) Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 341:1781–1788

    Article  PubMed  CAS  Google Scholar 

  • Messing E, Manola J, Sarosdy M, Wilding G, Crawford ED (2003) Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node positive prostate cancer: results at 10 years of EST 3886 (abs 1480). J Urol 169:396

    Google Scholar 

  • Mettlin CJ, Murphy GP, Rosenthal DS, Menck HR (1998) The National Cancer Data Base report on prostate carcinoma after the peak in incidence rates in the U.S. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 83:1679–1684

    Article  PubMed  CAS  Google Scholar 

  • Migliari R, Muscas G, Murru M, Verdacchi T, De Benedetto G, De Angelis M (1999) Antiandrogens: a summary review of pharmacodynamic properties and tolerability in prostate cancer therapy. Arch Ital Urol Androl 71:293–302

    PubMed  CAS  Google Scholar 

  • Nishiyama T, Kanazawa S, Watanabe R, Terunuma M, Takahashi K (2004) Influence of hot flashes on quality of life in patients with prostate cancer treated with androgen deprivation therapy. Int J Urol 11:735–741

    Article  PubMed  Google Scholar 

  • Paisey RB, Kadow C, Bolton C, Hartog M, Gingell JC (1986) Effects of cyproterone acetate and a long-acting LHRH analogue on serum lipoproteins in patients with carcinoma of the prostate. J R Soc Med 79:210–211

    PubMed  CAS  Google Scholar 

  • Pilepich MV, Winter K, Lawton CA, Krish RE, Wolkov HB, Movsas B, Hug EB, Asbell SO, Grignon D (2005) Androgen suppression adjuvant to definitive radiotherapy in carcinomas of the prostate—long term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys 61:1285–1290

    PubMed  CAS  Google Scholar 

  • Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC (1999) Natural history of progression after PSA elevation following radical prostatectomy. JAMA 281:1591–1597

    Article  PubMed  CAS  Google Scholar 

  • Saltzstein D, Sieber P, Morris T, Gallo J (2005) Prevention and management of bicalutamide-induced gynecomastia and breast pain: randomized endocrinologic and clinical studies with tamoxifen and anastrozole. Prostate Cancer Prostatic Dis 8:75–83

    Article  PubMed  CAS  Google Scholar 

  • Schröder FH, Collette L, De Reijke TM, Whelan P, members of the EORTC Genitourinary Group (2000) Prostate cancer treated by anti-androgens: is sexual function preserved? Br J Cancer 82:283–290

    Google Scholar 

  • Schröder FH, Whelan P, De Reijke TM, Kurth KH, Pavone-Macaluso M, Mattelaer J, van Velthoven RF, Debois M, Collette L (2004) Metastatic prostate cancer treated by flutamide versus cyproterone acetate. Final analysis of the “European Organization for Research and Treatment of Cancer” (EORTC) Protocol 30892. Eur Urol 45:457–464

    Article  PubMed  CAS  Google Scholar 

  • Shipley WU, Thames HD, Sandler HM, Hanks GE, Zietman AL, Perez CA, Kuban DA, Hancock SL, Smith CD (1999) Radiation therapy for clinically localized prostate cancer. A multi-institutional pooled analysis. JAMA 281:1598–1604

    Article  PubMed  CAS  Google Scholar 

  • Sieber PR, Keiller DL, Kahnoski RJ, Gallo J, McFadden S (2004) Bicalutamide 150 mg maintains bone mineral density during monotherapy for localized or locally advanced prostate cancer. J Urol 171:2272–2276

    Article  PubMed  CAS  Google Scholar 

  • Smith MR, Goode M, Zietman AL, McGovern FJ, Lee H, Finkelstein JS (2004) Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition. J Clin Oncol 22:2546–2553

    Article  PubMed  CAS  Google Scholar 

  • 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 29:47–54

    PubMed  CAS  Google Scholar 

  • Tyrrell CJ, Payne H, Tammela TL, Bakke A, Lodding P, Goedhals L, Van Erps P, Boon T, Van De Beek C, Andersson SO, Morris T, Carroll K (2004) Prophylactic breast irradiation with a single dose of electron beam radiotherapy (10 Gy) significantly reduces the incidence of bicalutamide-induced gynecomastia. Int J Radiat Oncol Biol Phys 60:476–483

    PubMed  Google Scholar 

  • Van Poppel H, Tyrrell CJ, Haustermans K, Cangh PV, Keuppens F, Colombeau P, Morris T, Garside L (2005) Efficacy and tolerability of radiotherapy as treatment for bicalutamide-induced gynaecomastia and breast pain in prostate cancer. Eur Urol 47:587–592

    Article  PubMed  Google Scholar 

  • Verhelst J, Denis L, Van Vliet P, Van Poppel H, Braeckman J, Van Cangh P, Mattelaer J, D’Hulster D, Mahler Ch (1994) Endocrine profiles during administration of the new non-steroidal anti-androgen Casodex in prostate cancer. Clin Endocrinol (Oxf) 41:525–530

    Article  CAS  Google Scholar 

  • de Voogt HJ, Smith PH, Pavone-Macaluso M, De Pauw M, Suciu S, members of the European Organization for Research on Treatment of Cancer Urological Group (1986) Cardiovascular side effects of diethylstilbestrol, cyproterone acetate, medroxyprogesterone acetate and estramustine phosphate used for the treatment of advanced prostatic cancer: results from European Organization for Research on Treatment of Cancer trials 30761 and 30762. J Urol 135:303–307

    Google Scholar 

  • Wirth MP, Weissbach L, Marx FJ, Heckl W, Jellinghaus W, Riedmiller H, Noack B, Hinke A, Froehner M (2004a) Prospective randomized trial comparing flutamide as adjuvant treatment versus observation after radical prostatectomy for locally advanced, lymph node-negative prostate cancer. Eur Urol 45:267–270

    Article  CAS  Google Scholar 

  • Wirth MP, See WA, McLeod D, Iversen P, Morris T, Carroll K, Casodex Early Prostate Cancer Trialists’ Group (2004b) Bicalutamide 150 mg in addition to standard care in patients with localized or locally advanced prostate cancer: results from the second analysis of the early prostate cancer program at median followup of 5.4 years. J Urol 172:1865–1870

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Acknowledgments

The EPC program was funded by AstraZeneca. Dr. Sarah Goodger of Complete Medical Group provided medical writing support on behalf of AstraZeneca.

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Correspondence to David Gillatt.

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Gillatt, D. Antiandrogen treatments in locally advanced prostate cancer: are they all the same?. J Cancer Res Clin Oncol 132 (Suppl 1), 17–26 (2006). https://doi.org/10.1007/s00432-006-0133-5

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