Skip to main content

Advertisement

SpringerLink
Log in

What implications do the tolerability profiles of antiandrogens and other commonly used prostate cancer treatments have on patient care?

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Increased awareness of prostate cancer has led to earlier initiation of therapy, and the potential for a longer duration of treatment has led to a stronger emphasis on tolerability. Historically, the mainstay of treatment of hormone-sensitive prostate cancer has been castration-based therapy, but antiandrogens are now emerging as an alternative. This article reviews the tolerability profiles of antiandrogens as well as other existing treatments for prostate cancer and examines their implications on patient care.

Methods

A search of online literature databases was conducted to identify recent articles and studies (1990–2006) that have reported adverse effects associated with treatment approaches for men with prostate cancer. The therapies reviewed here include castration, antiandrogens, a combination of castration and antiandrogens (CAB), estrogens, and chemotherapy.

Results

Castration offers significant clinical benefits when used as monotherapy or as adjuvant therapy; however, it is associated with loss of bone mineral density, and a reduction in physical activity and sexual function, which can have a negative impact on quality of life. Detrimental effects on muscle mass, fat deposition, and cognitive function have also been reported. Recent data suggest that the non-steroidal antiandrogen, bicalutamide, confers a significant overall survival benefit when used as adjuvant to radiotherapy in patients with locally advanced disease. However, the survival data for bicalutamide are not as extensive as those available for LHRH agonists. Although they do not appear to have a significant impact on sexual and physical activity, non-steroidal antiandrogens are frequently associated with gynecomastia and breast pain, and some are associated with diarrhea. Estrogens have been used in patients with androgen-independent prostate cancer; however, cardiovascular toxicity has restricted their use. In patients whose prostate cancer has become hormone-refractory, treatment options include chemotherapeutic agents, such as docetaxel and mitoxantrone.

Conclusions

It is important for physicians to discuss the adverse effects of all the available treatment options with patients so that a therapy can be selected to meet their expectations in terms of overall survival and tolerability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Akaza H, Yamaguchi A, Matsuda T, Igawa M, Kumon H, Soeda A, Arai Y, Usami M, Naito S, Kanetake H, Ohashi Y (2004) 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 34:20–28

    Article  PubMed  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 (accessed 19 December 2005, through http://www.uroweb.nl/files/uploaded_files/2005Prostate%20Cancer.pdf)

  • 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 

  • 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 

  • Bruchovsky N, Goldenberg SL, Akakura K, Rennie PS (1993) Luteinizing hormone-releasing hormone agoinsts in prostate cancer. Elimination of flare reaction by pretreatment with cyproterone acetate and low-dose diethylstilbestrol. Cancer 72:1685–1691

    Article  PubMed  CAS  Google Scholar 

  • Bruun E, Frimodt-Moller C (1996) The effect of buserelin versus conventional antiandrogenic treatment in patients with T2-4NXM1 prostatic cancer. A prospective, randomized multicentre phase III trial. The “Danish Buserelin Study Group”. Scand J Urol Nephrol 30:291–297

    Article  PubMed  CAS  Google Scholar 

  • Cassileth BR, Soloway MS, Vogelzang NJ, Chou JM, Schellhammer PD, Seidmon EJ, Kennealey GT, members of the Zoladex Prostate Cancer Study Group (1992) Quality of life and psychosocial status in stage D prostate cancer. Qual Life Res 1:323–330

    Google Scholar 

  • Chatelain C, Rousseau V, Cosaert J (1994) French multicentre trial comparing Casodex (ICI 176,334) monotherapy with castration plus nilutamide in metastatic prostate cancer: a preliminary report. Eur Urol 26(suppl 1):10–14

    PubMed  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 

  • Di Lorenzo G, Perdona S, De Placido S, D’Armiento M, Gallo A, Damiano R, Pingitore D, Gallo L, De Sio M, Autorino R (2005) Gynecomastia and breast pain induced by adjuvant therapy with bicalutamide after radical prostatectomy in patients with prostate cancer: the role of tamoxifen and radiotherapy. J Urol 174:2197–2203

    Article  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 

  • Green HJ, Pakenham KI, Headley BC, Yaxley J, Nicol DL, Mactaggart PN, Swanson CE, Watson RB, Gardiner RA (2004) Quality of life compared during pharmacological treatments and clinical monitoring for non-localized prostate cancer: a randomized controlled trial. BJU Int 93:975–979

    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, 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, 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 

  • Jenkins V, Fallowfield L, Edginton T, Payne H, Hamilton E (2005) Preferences of healthy men for two different endocrine treatment options offered for locally advanced prostate cancer. Curr Med Res Opin 21:1329–1335

    Article  PubMed  CAS  Google Scholar 

  • Kaisary AV, Tyrrell CJ, Peeling WB, Griffiths K, on behalf of Study Group (1991) Comparison of LHRH analogue (Zoladex) with orchiectomy in patients with metastatic prostatic carcinoma. Br J Urol 67:502–508

    Google Scholar 

  • Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V, Trump D, Winer EP, Vogelzang NJ (1999) Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. J Clin Oncol 17:2506–2513

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Klotz L (2004) Active surveillance with selective delayed intervention: using natural history to guide treatment in good risk prostate cancer. J Urol 172:S48–S50

    Article  PubMed  Google Scholar 

  • McLeod D, Zinner N, Tomera K, Gleason D, Fotheringham N, Campion M, Garnick MB (2001) A phase 3, multicenter, open-label, randomized study of abarelix versus leuprolide acetate in men with prostate cancer. Urology 58:756–761

    Article  PubMed  CAS  Google Scholar 

  • 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. J Urol 169:396, abs 1480

    Google Scholar 

  • Oh WK (2002) Secondary hormonal therapies in the treatment of prostate cancer. Urology 60(Suppl 3A):87–93

    Article  PubMed  Google Scholar 

  • Peeling WB (1989) A comparison between surgical orchidectomy and the LHRH agoinst ‘Zoladex’ (ICI 188630) in the treatment of metastatic cancer of the prostate. Prog Clin Biol Res 303:41–45

    PubMed  CAS  Google Scholar 

  • Pether M, Goldenberg SL, Bhagirath K, Gleave M (2003) Intermittent androgen suppression in prostate cancer: an update of the Vancouver experience. Can J Urol 10:1809–1814

    PubMed  Google Scholar 

  • Petrylak DP (2005) Chemotherapy for androgen-independent prostate cancer. World J Urol 23:10–13

    Article  PubMed  CAS  Google Scholar 

  • Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED (2004) Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351:1513–1520

    Article  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 

  • Prostate Cancer Trialists’ Collaborative Group (2000) Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet 355:1491–1498

    Article  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 

  • Sarosdy MF, Schellhammer PF, Soloway MS, Vogelzang NJ, Crawford ED, Presti J, Chodak GW, Mitchell P, Porter L (1999) Endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of goserelin acetate administered every 13 weeks to patients with advanced prostate cancer. BJU Int 83:801–806

    Article  PubMed  CAS  Google Scholar 

  • Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Jones Schellenger J, Kolvenbag GJCM, for the Casodex Combination Study Group (1997) 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. Urology 50:330–336

    Google Scholar 

  • Scherr DS, Pitts WR Jr (2003) The nonsteroidal effects of diethylstilbestrol: the rationale for androgen deprivation therapy without estrogen deprivation in the treatment of prostate cancer. J Urol 170:1703–1708

    Article  PubMed  CAS  Google Scholar 

  • Schmitt B, Wilt TJ, Schellhammer PF, DeMasi V, Sartor O, Crawford ED, Bennett CL (2001) Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer: a systematic review. Urology 57:727–732

    Article  PubMed  CAS  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 

  • Schroder FH, Kurth KH, Fossa SD, Hoekstra W, Karthaus PP, Debois M, Collette L (2004) Early versus delayed endocrine treatment of pN1-3 M0 prostate cancer without local treatment of the primary tumor: results of European Organisation for the Research and Treatment of Cancer 30846–a phase III study. J Urol 172:923–927

    Article  PubMed  Google Scholar 

  • Sculpher M, Bryan S, Fry P, De Winter P, Payne H, Emberton M (2004) Patients’ preferences for the management of non-metastatic prostate cancer: discrete choice experiment. BMJ 328:382

    Article  PubMed  Google Scholar 

  • See WA, Wirth MP, McLeod DG, Iversen P, Klimberg I, Gleason D, Chodak G, Montie J, Tyrrell C, Wallace DMA, Delaere KPJ, Vaage S, Tammela TLJ, Lukkarinen O, Persson B-E, Carroll K, Kolvenbag GJCM, on behalf of the Casodex Early Prostate Cancer Trialist Group (2002) Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program. J Urol 168:429–435

    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, McGovern FJ, Zietman AL, Fallon MA, Hayden DL, Schoenfeld DA, Kantoff PW, Finkelstein JS (2001) Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 345:948–955

    Article  PubMed  CAS  Google Scholar 

  • Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N (2003) Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol 169:2008–2012

    Article  PubMed  CAS  Google Scholar 

  • Stephenson RA (2002) Prostate cancer trends in the era of prostate-specific antigen. An update of incidence, mortality, and clinical factors from the SEER database. Urol Clin North Am 29:173–181

    Article  PubMed  Google Scholar 

  • Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CML, Murphy KC (1996) Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 14:1756–1764

    PubMed  CAS  Google Scholar 

  • Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502–1512

    Article  PubMed  CAS  Google Scholar 

  • Trachtenberg J, Gittleman M, Steidle C, Barzell W, Friedel W, Pessis D, Fotheringham N, Campion M, Garnick MB, the Abarelix Study Group (2002) A phase 3, multicenter, open label, randomized study of abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer. J Urol 167:1670–1674

    Google Scholar 

  • Tyrrell CJ, Altwein JE, Klippel F, Varenhorst E, Lunglmayer G, Boccardo F, Holdaway IM, Haefliger J-M, Jordaan JP, Sotarauta M, of the International Prostate Cancer Study Group (1998a) An international, multicentre, randomised trial comparing ‘Zoladex’ (goserelin acetate) with maximum androgen blockade (MAB) in advanced prostate cancer: Final survival results. EAU March 21–25, Barcelona, 1998 183:

  • Tyrrell CJ, Kaisary AV, Iversen P, Anderson JB, Baert L, Tammela T, Chamberlain M, Webster A, Blackledge G (1998b) A randomised comparison of ‘Casodex’™ (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol 33:447–456

    Article  CAS  Google Scholar 

  • Tyrrell CJ, Payne H, Tammela TL, Bakke A, Lodding P, Goedhals L, Van Erps P, Boon T, Van De BC, 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 

  • Vogelzang NJ, Chodak GW, Soloway MS, Block NL, Schellhammer PF, Smith Jr JA, Caplan RJ, Kennealey GT, for the Zoladex Prostate Study Group (1995) Goserelin versus orchiectomy in the treatment of advanced prostate cancer: final results of a randomized trial. Urology 46:220–226

    Google Scholar 

  • Weckermann D, Harzmann R (2004) Hormone therapy in prostate cancer: LHRH antagonists versus LHRH analogues. Eur Urol 46:279–283

    Article  PubMed  CAS  Google Scholar 

  • Widmark A, Fosså SD, Lundmo P, Damber J-E, Vaage S, Damber L, Wiklund F, Klepp O (2003) Does prophylactic breast irradiation prevent antiandrogen-induced gynecomastia? Evaluation of 253 patients in the randomized Scandinavian trial SPCG-7/SFUO-3. Urology 61:145–151

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Chris Rapier of Complete Medical Group, who provided medical writing support on behalf of AstraZeneca.

Author information

Authors and Affiliations

  1. Department of Oncology and Palliative Medicine, Cardiff University, Velindre Hospital, Whitchurch, Cardiff, CF14 2TL, UK

    Malcolm Mason

Authors
  1. Malcolm Mason
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Malcolm Mason.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mason, M. What implications do the tolerability profiles of antiandrogens and other commonly used prostate cancer treatments have on patient care?. J Cancer Res Clin Oncol 132 (Suppl 1), 27–35 (2006). https://doi.org/10.1007/s00432-006-0134-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-006-0134-4

Keywords

Search

Navigation