Many options involving the AR, androgens, and their antagonists are available for the treatment of PCa (Fig. 1). Numerous clinical studies have shown equivalent effects on therapeutic benefits by different hormonal treatment strategies. Each treatment strategy/hormonal agent has favorable and unfavorable effects (Table 1). Patients with advanced PCa will clearly benefit from androgen deprivation-based treatments for symptom palliation and improvement of their QOL. However, whether these therapies prolong survival when administered before there are symptoms caused by disease progression remains controversial. Thus, despite a number of previous clinical and experimental studies, finding suitable patients, timing of, and options for hormonal therapy remain problem-atic.121 Data from recent studies support the premise that an earlier treatment in patients' disease course likely leads to better outcomes,82,84,92 but it is not easy to predict the best timing of hormonal therapy for patients with asymptomatic advanced disease. Observation may still be a reasonable choice for these patients.
Currently, available options for hormonal therapy almost never lead to cures in patients with advanced PCa because these patients eventually develop androgen-independent tumors. In addition, another type of failure of hormonal therapy, antiandrogen withdrawal syndrome, has been observed in a significant number (15%—80%) of patients treated with CAB. Although the exact mechanisms for androgen-independent PCa and antiandrogen withdrawal syndrome are far from being fully understood, possible mechanisms were discussed in recent review papers.122'123 To improve overall survival of patients with advanced PCa, novel treatment strategies that prolong the androgen-dependent state, but will not induce antiandrogen withdrawal syndrome, and that are effective against androgen-independent disease, need to be identified. Furthermore, it may be necessary to explore more individualized approaches, such as selectively blocking the activated AR pathway in cancer cells. Finally, second-line hormonal therapy and PCa chemoprevention using hormonal therapy are other interesting topics that are not discussed in this chapter (please refer to Chapter 6 in this volume).
1. Huggins C, Hodges CV (1941) Studies on prostatic cancer. I. The effects of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1:293-297.
2. Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun M (2003) Cancer statistics, 2003. CA Cancer J Clin 53:5-26.
3. Chang C, Kokontis J, Liao S (1988) Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science 240:324-326.
4. Chang C, Saltzman A, Yeh S, Young W, Keller E, Lee H-J, Wang C, Mizokami A (1995) Androgen receptor: An overview. Crit Rev Eukaryot Gene Expr 5:97-125.
5. Heinlein CA, Chang C (2002) Androgen receptor (AR) coregulators: An overview. Endocr Rev 23:175-200.
6. Russell DW, Wilson JD (1994) Steroid 5a-reductase: Two genes/two enzymes. Annu Rev Biochem 63:25-61.
7. Geller J (1985) Rationale for blockade of adrenal as well as testicular androgens in the treatment of advanced prostate cancer. Semin Oncol 12(Suppl 1):28-35.
8. Culig Z, Hobisch A, Cronauer MV Cato ACB, Hittmair A, Radmayr C, Eberle J, Bartsch G, Klocker H (1993) Mutant androgen receptor detected in an advanced-stage prostatic carcinoma is activated by adrenal androgens and progesterone. Mol Endocrinol 7:1541-1550.
9. Miyamoto H, Yeh S, Lardy H, Messing E, Chang C (1998) A5-androstenediol is a natural hormone with androgenic activity in human prostate cancer cells. Proc Natl Acad Sci USA 95:11083-11088.
10. Miyamoto H, Chang C (2000) Antiandrogens fail to block androstenedione-mediated mutated androgen receptor transactivation in human prostate cancer cells. Int J Urol 7:32-34.
11. Maatman TJ, Gupta MK, Montie JE (1985) Effectiveness of castration versus intravenous estrogen therapy in producing rapid endocrine control of metastatic cancer of the prostate. J Urol 133:620-621.
12. Byar DP (1973) The Veterans Administration Cooperative Urological Research Group's studies of cancer of the prostate. Cancer 32:1126-1130.
13. Byar DP, Corle DK (1988) Hormone therapy for prostate cancer: Results of the Veterans Administration Cooperative Urological Research Group studies. J Natl Cancer Inst Monogr (NCI Monogr) 7:165-170.
14. Chadwick DJ, Gillatt DA, Gingell JC (1991) Medical or surgical orchiectomy: the patients' choice. BMJ 302:572.
15. Fossa SD, Aass N, Opjordsmoen S (1994) Assessment of quality of life in patients with prostate cancer. Semin Oncol 21:657-661.
16. Clark JA, Wray NP, Ashton CM (2001) Living with treatment decisions: Regrets and quality of life among men treated for metastatic prostate cancer. J Clin Oncol 19:72-80.
17. The Leuprolide Study Group (1984) Leuprolide versus diethylstilbestrol for metastatic prostate cancer. N Engl J Med 311:1281-1286.
18. deVoogt HJ, Smith PH, Pavone-Macaluso M, de Pauw M, Suciu S, and 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 prostate cancer: Results from European Organization for Research on Treatment of Cancer Trials 30761 and 30762. J Urol 135:303-307.
19. Emtage LA, Trethowan C, Kelly K, Arkell D, Wallace DM, Hughes M, Hay A, Blacklock R, Jones M, Rouse A, Farrar D, Young C, Blackledge G (1989) A phase III open randomized study of Zoladex 3.6mg depot vs. DES 3 mg per day in untreated advanced prostate cancer: A West Midlands Urological Research Group Study. Prog Clin Biol Res 303:47-52.
20. Citrin DL, Resnick MI, Guiman P, Al-Bussam N, Scott M, Gau TL, Kennealey GT (1991) A comparison of Zoladex® and DES in the treatment of advanced prostate cancer: Results of randomized, multicenter trial. Prostate 18:139-146.
21. Chang A, Yeap B, Davis T, Blum R, Hahn R, Khanna O, Fisher H, Rosenthal J, White 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.
22. Robinson MR, Smith P, Richards B, Newling DW, de Pauw M, Sylvester R (1995) The final analysis of the EORTC genito-urinary tract cancer cooperative group phase III clinical trial (protocol 30805) comparing orchiec-tomy, orchiectomy plus cyproterone acetate and low dose stilboestrol in the management of metastatic carcinoma of the prostate. Eur Urol 28:273-283.
23. Orlando M, Chacon M, Salum G, Chacon DR (2000) Low-dose continuous oral fosfestrol is highly active in 'hormone-refractory' prostate cancer. Ann Oncol 11:177-181.
24. Malkowicz SB (2001) The role of diethylstilbestrol in the treatment of prostate cancer. Urology 58(Suppl 2A):108-113.
25. Kitahara S, Yoshida K, Ishizaka K, Kageyama Y, Kawakami S, Tsuji T, Oshima H (1997) Stronger suppression of serum testosterone and FSH levels by a synthetic estrogen than by castration or an LH-RH agonist. Endocr J 44:527-532.
26. Kitahara S, Umeda H, Yano M, Koga F, Sumi S, Moriguchi H, Hosoya Y, Honda M, Yoshida K (1999) Effects of intravenous administration of high dose-diethylstilbestrol diphosphate on serum hormonal levels in patients with hormone-refractory prostate cancer. Endocr J 46:659-664.
27. Mangan FR, Neal GE, Williams DC (1967) The effects of diethylstilboestrol and castration on the nucleic acid and protein metabolism of rat prostate gland. Biochem J 104:1075-1081.
28. Ferro MA, Heinemann D, Smith PJB, Symes MO (1988) Effect of stilboe-strol and testosterone on the incorporation of 75selenomethionine by prosta-tic carcinoma cells. Br J Urol 62:166-172.
29. Robertson CN, Roberson KM, Padilla GM, O'Brien ET, Cook JM, Kim L-S, Fine RC (1996) Induction of apoptosis by diethylstilbestrol in hormone-insensitive prostate cancer cells. J Natl Cancer Inst 88:908-917.
30. Castle EP, Thrasher JB (2002) The role of soy phytoestrogens in prostate cancer. Urol Clin North Am 29:71-81.
31. Lau KM, LaSpina M, Long J, Ho SM (2000) Expression of estrogen receptor (ER)-a and ER-ß in normal and malignant prostatic epithelial cells: Regulation by methylation and involvement in growth regulation. Cancer Res 60:3175-3182.
32. Latil A, Bieche I, Vidaud D, Lidereau R, Berthon P, Cussenot O, Vidaud M (2001) Evaluation of androgen, estrogen (ERa and ERß), and progesterone receptor expression in human prostate cancer by real-time quantitative reverse transcription-polymerase chain reaction assays. Cancer Res 61:1919-1926.
33. Signoretti S, Loda M (2001) Estrogen receptor (3 in prostate cancer: Brake pedal or accelerator? Am J Pathol 159:13-16.
34. Yeh S, Miyamoto H, Shima H, Chang C (1998) From estrogen to androgen receptor: A new pathway for sex hormones in prostate. Proc Natl Acad Sci USA 95:5527-5532.
35. Labrie F, Belanger A, Susan L, Labrie C, Simard J, Luu-The V Diamond P, Gomez J-L, Candas B (1996) Histroy of LHRH agonist and combination therapy in prostate cancer. Endocr-Rel Cancer 3:243-278.
36. Dondi D, Limonta P, Moretti RM, Marelli MM, Garattini E, Motta M (1994) Antiproliferative effects of luteinizing hormone-releasing hormone (LHRH) agonists on human androgen-independent prostate cancer cell line DU 145: Evidence for an autocrine-inhibitory LHRH loop. Cancer Res 54:4091-4095.
37. Koppan M, Nagy A, Schally AV, Plonowski A, Halmos G, Arencibia JM, Groot K (1999) Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 inhibits the growth of PC-82 human prostate cancer in nude mice. Prostate 38:151-158.
38. Denis L (1998) European Organization for Research and Treatment of Cancer (EORTC) prostate cancer trials, 1976-1996. Urology 51(Suppl 5A): 50-57.
39. Seidenfeld J, Samson DJ, Hasselblad V Aronson N, Albertsen PC, Bennett CL, Wilt TJ (2000) Single-therapy androgen suppression in men with advanced prostate cancer: A systematic review and meta-analysis. Ann Intern Med 132:566-577.
40. Tunn UW, Bargelloni U, Cosciani S, fiaccavento G, Guazzieri S, Pagano F (1998) Comparison of LH-RH analogue 1-month depot and 3-month depot by their hormone levels and pharmacokinetic profile in patients with advance prostate cancer. Urol Int 60(Suppl 1):9-16.
41. Stege R (2000) Potential side effects of endocrine treatment of long duration in prostate cancer. Prostate Suppl 10(Suppl):38-42.
42. Bubley GJ (2001) Is the flare phenomenon clinically significant? Urology 58(Suppl 2A):5-9.
43. Labrie F, Dupont A, Belanger A, Lachance R (1987) Flutamide eliminates the risk of disease flare in prostatic cancer patients treated with a luteinizing hormone-releasing hormone agonist. J Urol 138:804-806.
44. Cook T, Sheridan WP (2000) Development of GnRH antagonists for prostate cancer: New approaches to treatment. Oncologist 5:162-168.
45. Stricker HJ (2001) Luteinizing hormone-releasing hormone antagonists in prostate cancer. Urology 58(Suppl 2A):24-27.
46. McLeod D, Zinner N, Tomera K, Gleason D, Fotheringham N, Campion M, Garnick MB for the Abarelix Study Group (2001) A phase 3, multicenter, open-label, randomized study of abarelix versus leuprolide acetate in men with prostate cancer. Urology 58:756-761.
47. Tomera K, Gleason D, Gittelman M, Moseley W, Zinner N, Murdoch M, Menon M, Campion M, Garnick MB for the Abarelix Study Group (2001) The Gonadotropin-releasing hormone antagonist abarelix depot versus luteinizing hormone releasing hormone agonists leuprolide or goserelin: Initial results of endocrinological and biochemical efficacies in patients with prostate cancer. J Urol 165:1585-1589.
48. Trachtenberg J, Gittleman M, Steidle C, Barzell W, Friedel W, Pessis D, Fotheringham N, Campion M, Garnick MB and 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.
49. Labrie F, Dupont A, Giguere M, Borsanyi J-P, Lacouraere Y, Montette G, Emond J, Bergeron N (1998) Benefits of combination therapy with flutamide in patients relapsing after castration. Br J Urol 61:341-346.
50. Sandow J, von Rechenberg W, Engelbart K (1988) Pharmacological studies on androgen suppression in therapy of prostate carcinoma. Am J Clin Oncol 11(Suppl 1):S6-S10.
51. Prostate Cancer Trialists' Collaborative Group (2000) Maximum androgen blockade in advanced prostate cancer: An overview of the randomised trials. Lancet 355:1491-1498.
52. Boccardo F (2000) Hormone therapy of prostate cancer: Is there a role for antiandrogen monotherapy? Crit Rev Oncol Hematol 35:121-132.
53. Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr A, Blumenstein BA, Davis MA, Goodman PJ. (1989) A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med 321:419-424.
54. Boccardo F, Pace M, Rubagotti A, Guarneri D, Decensi A, Oneto F, Martorana G, Giuliani L, Selvaggi F, Battaglia M, Ponti UD, Petracco S, Cortellini P, Ziveri M, Ferraris U, Bruttini GP, Epis R, Comeri G, Gallo G, and other participants in the Italian Prostatic Cancer Project (PONCAP)
Study Group (1993) Goserelin acetate with or without flutamide in the treatment of patients with locally advanced or metastatic prostate cancer. Eur J Cancer 29:1088-1093.
55. Denis LJ, Whelan P, de Moura JCL, Newling D, Bono A, De Pauw M, Sylvester R (1993) Goserelin acetate and flutamide versus bilateral orchiectomy: A phase III EORTC trial (30853). Urology 42:119-132.
56. Janknegt RA, Abbou CC, Bartoletti R Bernstein-Hahn L, Bracken B, Brisset JM, Da Silva FC, Chisholm G, Crawford ED, Debruyne FMJ, Dijkman GD, Frick J, Goedhals L, Knönagel H, Venner PM (1993) Orchiectomy and nilutamide or placebo as treatment of metastatic prostatic cancer in a multinational double-blind randomized trial. J Urol 149:77-83.
57. Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ, Wilding G, Sears K, Culkin DJ, Thompson Jr IM, Lowe BA (1998) Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med 339:1036-1042.
58. Schmitt B, Wilt TJ, Schellhammer PF, De Masi V Sartor O, Crawford ED, Bennett CL (2001) Combined androgen blockade with nonsteroidal antian-drogens for advanced prostate cancer: A systematic review. Urology 57:727-732.
59. Iversen P (2002) Antiandrogen monotherapy: Indications and results. Urology 60(Suppl 3A):64-71.
60. Delaere KPJ, Van Thillo EL (1991) Flutamide monotherapy as primary treatment in advanced prostatic carcinoma. Semin Oncol 18(Suppl 6):13-18.
61. Decensi AU, Boccardo F, Guarneri D, Positano N, Parletti MC, Costantini M, Martorano 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.
62. Dole EJ, Holdsworth MT (1997) Nilutamide: An antiandrogen for the treatment of prostate cancer. Ann Pharmacother 31:65-75.
63. Bales GT, Chodak GW (1996) A controlled trial of bicalutamide versus castration in patients with advanced prostate cancer. Urology 47(Suppl 1A): 38-43.
64. Tyrrell CJ, Kaisary AV Iversen P, Anderson JB, Baert L, Tammela T, Chamberlain M, Webster A, Blackledge G (1998) A randomized comparison of 'Casodex'™ (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol 33:447-456.
65. Iversen P, Tyrrell CJ, Kaisary AV Anderson JB, Van Poppel H, Tammela TLJ, 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.
66. 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):10-14.
67. Boccardo F, Rubagotti A, Barichello M, Battaglia M, Carmignani G, Comeri G, Crucinni G, Dannino S, Delliponti U, Ditonno P, Ferraris V Lilliu S, Montetiore 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.
68. Katchen B, Buxbaum S (1975) Disposition of a new, nonsteroidal, antiandrogen, a,a,a-trifluoro-2-methy-4'-nitro-m-propionotoluidide (flutamide), in men following a single oral 200 mg dose. J Clin Endocrinol Metab 41:373-379.
69. McKillop D, Boyle GW, Cockshott ID, Jones DC, Phillips PJ, Yates RA (1993) Metabolism and enantioselective pharmacokinetics of Casodex in man. Xenobiotica 23:1241-1253.
70. 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 BE, Carroll K, Kolvenbag GJCM (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.
71. Goldenberg SL, Bruchovsky N (1991) Use of cyproterone acetate in prostate cancer. Urol Clin North Am 18:111-122.
72. de Voogt HJ (1992) The position of cyproterone acetate (CPA), a steroidal anti-androgen, in the treatment of prostate cancer. Prostate 4(Suppl):91-95.
73. Gleave ME, Sato N, Goldenberg SL, Stothers L, Bruchovsky N, Sullivan LD (1997) Neoadjuvant androgen withdrawal therapy decreases local recurrence rates following tumor excision in the Shionogi tumor model. J Urol 157:1727-1730.
74. Aus G, Abrahamsson P-A, Ahlgren G, Hugosson J, Lundberg S, Schain M, Schelin S, Pedersen K (2002) Three-month neoadjuvant hormonal therapy before radical prostatectomy: A 7-year follow-up of a randomized controlled trial. BJUInt 90:561-566.
75. Hurtado-Coll A, Goldenberg SL, Klotz L, Gleave ME (2002) Preoperative neoadjuvant androgen withdrawal therapy in prostate cancer: The Canadian experience. Urology 60(Suppl 3A):45-51.
76. Soloway MS, Pareek K, Sharifi R, Wajsman I, McLeod D, Wood Jr DP, Puras-Baez A and the Lupron Depot Neoadjuvant Prostate Cancer Study Group (2002) Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxM0 prostate cancer: 5-year results. J Urol 167:112-116.
77. Klotz LH, Goldenberg SL, Jewett MAS, Fradet Y, Nam R, Barkin J, Chin J, Chatterjee S and the Canadian Uro-oncology Group (2003) Long-term fol-lowup of a randomized trial of 0 versus 3 months of neoadjuvant androgen ablation before radical prostatectomy. J Urol 170:791-794.
78. Gleave ME, Goldenberg L, Chin JL, Warner J, Saad F, Klotz LH, Jewett M, Kassabian V Chetner M, Dupont C, Van Rensselaer S and the Canadian Uro-oncology Group (2001) Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: Biochemical and pathological effects. J Urol 166:500-507.
79. DeKernion JB, Neuwirth H, Stein A, Dorey F, Stenzl A, Hannah J, Blyth B (1990) Prognosis of patients with stage D1 prostate carcinoma following radical prostatectomy with and without early endocrine therapy. J Urol 144:700-703.
80. Zincke H, Bergstralh E, Larson-Keller JJ, Farrow GM, Myers RP, Lieber MM, Barrett DM, Rife CC, Gonochoroff NJ (1992) Stage D1 prostate cancer treated by radical prostatectomy and adjuvant hormonal treatment: evidence for favorable survival in patients with DNA diploid tumors. Cancer 70(Suppl 1):311-323.
81. Zincke H, Lau W, Bergstralh E, Blute ML (2001) Role of early adjuvant hormonal therapy after radical prostatectomy for prostate cancer. J Urol 166:2208-2215.
82. 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.
83. Walsh PC, DeWeese TL, Eisenberger MA (2001) A structures debate: Immediate versus deferred androgen suppression in prostate cancer: evidence for deferred treatment. J Urol 166:508-516.
84. Messing EM, Manola J, Yao J, Kiernan M, Crawford ED, Wilding G, di'SantAgnese PA (2004) Immediate vs. delayed hormonal therapy in patients with nodal positive prostate cancer who had undergone radical prostatectomy + pelvic lymphadenectomy: Results of central pathology review (Abstract). J Urol 171(Suppl 4):383.
85. Wirth M, Frohmüller H, Marx F, Bolten M, Theiß M (1997) Randomized multicenter trials on adjuvant flutamide therapy in locally advanced prostate cancer after radical surgery — Interim analysis of treatment effect and prognostic factors (Abstract). Br J Urol 80:263.
86. Zietman AL, Nakfoor BM, Prince EA, Gerweck LE (1997) The effect of androgen deprivation and radiation therapy on an androgen-sensitive murine tumor: An in vitro and in vivo study. Cancer J Sci Am 3:31-36.
87. Joon DL, Hasegawa M, Sikes C, Khoo VS, Terry NH, Zagars GK, Meistrich ML, Pollack A (1997) Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation. Int J Radiat Oncol Biol Phys 38:1071-1077.
88. Pollack A, Salem N, Ashoori F, Hachem P, Sangha M, von Eschenbach AC, Meistrich ML (2001) Lack of prostate cancer radiosensitization by androgen deprivation. Int J Radiat Oncol Biol Phys 51:1002-1007.
89. Hara I, Miyake H, Yamada Y, Takechi Y, Hara S, Gotoh A, Fujisawa M, Okada H, Arakawa S, Soejima T, Sugimura K, Kamidono S (2002) Neoadjuvant androgen withdrawal prior to external radiotherapy for locally advanced adenocarcinoma of the prostate. Int J Urol 9:322-328.
90. Granfors T, Tomic R, Bergh A, Rydh M, Lofroth PO, Widmark A (1999) After radiation testosterone stimulation is unable to increase growth in the dunning R3327-PAP prostate tumor. Urol Res 27:357-361.
91. Kaminski JM, Hanlon A, Joon DL, Meistrich M, Pollack A (2002) The effect of sequencing of androgen ablation and radiation on prostate cancer growth (Abstract). Int J Radiat Oncol Biol Phys 54(Suppl):190-191.
92. Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff R-O, Storme G, Bernier I, Kuten A, Sternberg C, Mattelaer J, Torecilla JL, Pfeffer JR (2002) Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomized trial. Lancet 360:103-108.
93. Pilepich MV Caplan R, Byhardt RW, Lawton CA, Gallagher MJ, Mesic JB, Hanks GE, Coughlin CT, Porter A, Shipley WU, Grignon D (1997) Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: Report of Radiation Therapy Oncology Group protocol 85-31. J Clin Oncol 15:1013-1021.
94. Pilepich MV, Winter K, Lawton C, Krisch RE, Wolkov H, Movsas B, Hug E, Asbell S, Grignon D (2003) Phase III trial of androgen suppression adjuvant to definitive radiotherapy. Long term results of RTOG study 85-31 (Abstract). Am Soc Clin Oncol 22:381A.
95. Shipley WU, Lu JD, Pilepich MV Heydon K, Roach III M, Wolkov HB, Sause WT, Rubin P, Lawton CA, Machtay M (2002) Effect of a short course of neoadjuvant hormonal therapy on the response to subsequent androgen suppression in prostate cancer patients with relapse after radiotherapy: A secondary analysis of the randomized protocol RTOG 86-10. Int J Radiat Oncol Biol Phys 54:1302-1310.
96. Horwitz EM, Winter K, Hanks GE, Lawton CA, Russell AH, Machtay M (2001) Subset analysis of RTOG 85-31 and 86-10 indicates an advantage for long-term vs. short-term adjuvant hormones for patients with locally advanced nonmetastatic prostate cancer treated with radiation therapy. Int J Radiat Oncol Biol Phys 49:947-956.
97. Hanks GE, Lu JD, Machtay M, Venkatesan VM, Pinover WH, Byhardt RW, Rosenthal SA (2000) RTOG protocol 92-02: A phase III trial of the use of long term total androgen suppression following neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate (Abstract). Int J Radiat Oncol Biol Phys 48(Suppl):112.
98. Lee WR (2002) The role of androgen deprivation therapy combined with prostate brachytherapy. Urology 60(Suppl 3A):39-44.
99. Eisenberger MA, Simon R, O'Dwyer PJ, Wittes RE, Friedman MA (1985) A reevaluation of nonhormonal cytotoxic chemotherapy in the treatment of prostatic carcinoma. J Clin Oncol 3:827-841.
100. Gilligan T, Kantoff PW (2002) Chemotherapy for prostate cancer. Urology 60(Suppl 3A):94-100.
101. Pettaway CA, Pisters LL, Troncoso P, Slaton J, Finn L, Kamoi K, Logothetis CJ (1999) Neoadjuvant chemotherapy and hormonal therapy followed by radical prostatectomy: Feasibility and preliminary results. J Clin Oncol 18:1050-1057.
102. Kreis W, Budman DR, Calabro A (1997) Unique synergism or antagonism of combinations of chemotherapeutic and hormonal agents in human prostate cancer cell lines. Br J Urol 79:196-202.
103. Martikainen P, Isaacs J (1990) Role of calcium in the programmed death of rat prostatic glandular cells. Prostate 17:175-187.
104. Wang H-G, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibazaki F, McKeon F, Babo T, Franke TF, Reed JC (1999) Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. Science 284:339-343.
105. Hussain A, Dawson N, Amin P, Naslund M, Engstrom C, Chen T (2001) Docetaxel followed by hormone therapy after failure of definitive treatments for clinically localized/locally advanced prostate cancer: Preliminary results. Semin Oncol 28(Suppl 15):22-31.
106. Langeler EG, Connie JC, van Uffelen CJC, Blankenstein MA, van Steenbrugge GJ, Mulder E (1993) Effect of culture conditions on androgen sensitivity of the human prostatic cancer cell line LNCaP. Prostate 23:213-223.
1G?. Akakura K, Bruchovsky N, Goldernberg SL, Rennie PS, Buckley AR, Sullivan LD (1993) Effects of intermittent androgen suppression on andro-gen-dependent tumors. Apoptosis and serum prostate-specific antigen. Cancer ?1:2?82-2?9G.
1G8. Sato N, Gleave ME, Bruchovsky N, Rennie PS, Goldenberg SL, Lange PH, Sullivan LD (1996) Intermittent androgen suppression delays progression to androgen-independent regulation of prostate-specific antigen gene in the LNCaP prostate tumor model. J Steroid Biochem Mol Biol 58:139-146.
1G9. Klotz LH, Herr HW, Morse MJ, Whitmore Jr WF (1986) Intermittent endocrine therapy for advanced prostate cancer. Cancer 58:2546-255G.
11G. Higano CS, Ellis W, Russel K, Lange PH (1996) Intermittent androgen suppression with leuprolide and flutamide for prostate cancer: A pilot study. Urology 48:8GG-8G4.
111. Crook JM, Szumacher E, Malone S, Huan S, Segal R (1999) Intermittent androgen suppression in the management of prostate cancer. Urology 53:53G-534.
112. Egawa S, Takashima R, Matsumoto K, Mizoguchi H, Kuwano S, Baba S (2GGG) A pilot study of intermittent androgen ablation in advanced prostate cancer in Japanese men. Jpn J Clin Oncol 3G:21-26.
113. Hurtado-Coll A, Goldenberg SL, Gleave ME, Klotz L (2GG2) Intermittent androgen suppression in prostate cancer: The Canadian experience. Urology 6G(Suppl 3A):52-56.
114. Hall MC, Fritzsch RJ, Sagalowsky AI, Ahrens A, Petty B, Roehrborn CG (1999) Prospective determination of the hormonal response after cessation of lutenizing hormone-releasing hormone agonist treatment in patients with prostate cancer. Urology 53:898-9G3.
115. Oefelein MG (2GG3) Health related quality of life using serum testosterone as the trigger to re-dose long acting depot luteinizing hormone-releasing hormone agonists in patients with prostate cancer. J Urol 169: 251-255.
116. Leibowitz RL, Tucker SJ (2GG1) Treatment of localized prostate cancer with intermittent triple androgen blockade: Preliminary results in 11G consecutive patients. Oncologist 6:177-182.
11?. Boyle P, Gould AC, Roehrborn CG (1996) Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology 48:398-4G5.
118. Ornstein DK, Smith DS, Andriole GL (1998) Biochemical response to testicular androgen ablation among patients with prostate cancer for whom flu-tamide and/or finasteride therapy failed. Urology 52:1G94-1G97.
119. Kirby R, Robertson C, Turkes A, Griffiths K, Denis LJ, Boyle P, Altwein J, Schröder F (1999) Finasteride in association with either flutamide or goserelin as combination hormonal therapy in patients with stage Ml carcinoma of the prostate gland. International Prostate Health Council (IPHC) Trial Study Group. Prostate 40:105-114.
120. McNulty AM, Audia JE, Bemis KG, Goode RL, Rocco VP, Neubauer BL (2000) Kinetic analysis of LY320236: competitive inhibitor of type I and non-competitive inhibitor of type II human steroid 5a-reductase. J Steroid Biochem Mol Biol 72:13-21.
121. Miyamoto H, Messing EM (2004) Early versus late hormonal therapy for prostate cancer. Curr Urol Rep 5:188-196.
122. Miyamoto H, Messing EM, Chang C (2004) Androgen deprivation therapy for prostate cancer: Current status and future prospects. Prostate, in press.
123. Miyamoto H, Rahman MM, Chang C (2004) Molecular basis for the antiandrogen withdrawal syndrome. J Cell Biochem 91:3-12.
Was this article helpful?