PTU - Polskie Towarzystwo Urologiczne
home page
current numbers
archival numbers
list of articles:
list przewodni/covering letter
editor
Scientific Committee
publisher
subscription
advertising
important links

Treatment approaches in patients with hormone resistant prostate cancer
Article published in Urologia Polska 2007/60/2.

authors

Theo M. de Reijke 1, Jean J.M.C.H. de la Rosette 1, Cora N. Sternberg 2
1 Department Of Urology Academic Medical Center, Amsterdam
2 Department of Medical Oncology San Camillo And Forlanini Hospitals, Rome

keywords

stercz, rak stercza, hormonooporność, chemioterapia, leczenie celowane

summary

Patients with locally advanced or metastatic prostate cancer are being treated with different forms of androgen deprivation therapy. The median time progression of this treatment approach ranges between 14 and 30 months. Following biochemical or objective progression the prostate cancer cells can still be androgen dependent for some time. The different treatment approaches in this disease stage are being described, including the working mechanism and possible application as second line treatment. Inevitably, however, the patient will progress to a hormone refractory prostate cancer stage. Recently, for the first time it was reported that docetaxel-based chemotherapy resulted in a modest survival benefit of approximately 2 months in patients with hormone refractory prostate cancer. The question is at this moment when to start this palliative chemotherapy and in which patients. Clearly, an improvement of these survival rates is necessary and several other approaches have been or are being investigated in patients with hormone refractory prostate cancer. The current stage of these treatment modalities are being discussed and put into clinical perspective. The great challenge will be to select these treatment modalities from the abundance of new agents that are in the pipeline of the pharmaceutical companies. Which of these targeted therapies have the biggest potential to be active as mono- or combination therapy in patients with prostate cancer? The goal of the treatment using the new treatment modalities will be to convert prostate cancer from a proliferative into a chronic disease. It is clear that selection of patients, using e. g. nomograms, genomics/proteomics, and side effect profile will then be very important. It is obvious that most of these new treatments will be tested in patients with hormone refractory prostate cancer, but once there is proven activity an earlier start of the treatment should be investigated. The setup of clinical trials with other endpoints (not survival) should be discussed in order to speed up the introduction of these new treatment modalities.

references

  1. Huggins C HC: The effects of castration of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941, 1, 293-297.
  2. Pronzato P, Rondini M: Hormonotherapy of advanced prostate cancer. Ann Oncol 2005, 16 Suppl 4, iv80-iv84.
  3. Kelly WK, Scher HI: Prostate specific antigen decline after antiandrogen withdrawal: the flutamide withdrawal syndrome. J Urol 1993, 149, 607-609.
  4. Taplin ME, Bubley GJ, Shuster TD et al: Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med 1995, 332, 1393-1398.
  5. Small EJ, Halabi S, Dawson NA et al: Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol 2004, 22, 1025-1033.
  6. Fowler JE, Jr., Pandey P, Seaver LE, Feliz TP: Prostate specific antigen after gonadal androgen withdrawal and deferred flutamide treatment. J Urol 1995, 154, 448-453.
  7. Scher HI, Liebertz C, Kelly WK et al: Bicalutamide for advanced prostate cancer: the natural versus treated history of disease. J Clin Oncol 1997, 15, 2928-2938.
  8. Joyce R, Fenton MA, Rode P et al: High dose bicalutamide for androgen independent prostate cancer: effect of prior hormonal therapy. J Urol 1998, 159, 149-153.
  9. Small EJ, Srinivas S: The antiandrogen withdrawal syndrome. Experience in a large cohort of unselected patients with advanced prostate cancer. Cancer 1995, 76, 1428-1434.
  10. Yagoda A, Petrylak D: Cytotoxic chemotherapy for advanced hormone-resistant prostate cancer. Cancer 1993, 71 (3 Suppl), 1098-1109.
  11. Collette L, van Andel G, Bottomley A et al: Is baseline quality of life useful for predicting survival with hormone-refractory prostate cancer? A pooled analysis of three studies of the European Organisation for Research and Treatment of Cancer Genitourinary Group. J Clin Oncol 2004, 22, 3877-3885.
  12. Taplin ME, Rajeshkumar B, Halabi S et al: Androgen receptor mutations in androgen-independent prostate cancer: Cancer and Leukemia Group B Study 9663. J Clin Oncol 2003, 21, 2673-2678.
  13. Chen CD, Welsbie DS, Tran C et al: Molecular determinants of resistance to antiandrogen therapy. Nat Med 2004, 10, 33-39.
  14. Taylor CD, Elson P, Trump DL: Importance of continued testicular suppression in hormone-refractory prostate cancer. J Clin Oncol 1993, 11, 2167-2172.
  15. Hussain M, Wolf M, Marshall E et al: Effects of continued androgen-deprivation therapy and other prognostic factors on response and survival in phase II chemotherapy trials for hormone-refractory prostate cancer: a Southwest Oncology Group report. J Clin Oncol 1994, 12, 1868-1875.
  16. Mazur AW, Thompson IM: Efficacy and morbidity of "channel" TURP. Urology 1991, 38, 526-528.
  17. Dearnaley DP: Radiotherapy of prostate cancer: established results and new developments. Semin Surg Oncol 1995, 11, 50-59.
  18. Hamdy FC, Williams JL: Use of dexamethasonefor ureteric obstruction in advanced prostate cancer: percutaneous nephrostomies can be avoided. BJU Int 1995, 75, 782-785.
  19. Fossa SD: Palliative pelvic radiotherapy in patient with hormone resistant prostate cancer. Prog Clin Biol Res 1987, 243, 479-485.
  20. Price P, Hoskin PJ, Easton D et al: Prospective randomised trial of single and multi-fractional radiotherapy schedules in the treatment of painful bony metastases. Radiother Oncol 1986, 65, 247-255.
  21. Jager PL, Kooistra A, Piers DA: Treatment with radioactive (89) strontium for patients with bone metastases from prostate cancer. BJU Int 2000, 86, 929-934.
  22. Salazar OM, Sandhu T, da Motta NW et al: Fractionated half-body irradiation (HBI) for the rapid palliation of widespread symptomatic, metastatic, bone disease: a randomized Phase III trial of the International Atomic Energy Agency (IAEA). Int J Radiat Oncol Biol Phys 2001, 50, 765-775.
  23. Huddart RA, Rajan B, Law M et al: Spinal cord compression in prostate cancer: treatment outcome and prognostic factors. Radiother Oncol 1997, 44, 229-236.
  24. Kunan DA, El-Mahdi AM, Sigfred SV et al: Characteristics of spinal cord compression in adenocarcinoma of the prostate. Urology 1986, 28, 364-369.
  25. Dawson NA: Apples and oranges: building a consensus for standardized eligibility criteria and end points in prostate cancer clinical trials. J Clin Oncol 1998, 16, 3398-3405.
  26. Scher HI, Steineck G, Kelly WK: Hormone-refractory (D3) prostate cancer: refining the concept. Urology 1995, 46, 142-148.
  27. Tannock IF, de Wit R, Berry WR et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004, 351, 1502-1512.
  28. Kelly WK, Scher HI, Mazumdar M et al: Prostate-specific antigen as a measure of disease outcome in metastatic hormone-refractory prostate cancer. J Clin Oncol 1993, 11, 607-615.
  29. Bubley GJ, Carducci M, Dahut W et al: Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol 1999, 17, 3461-3467.
  30. Therasse P, Arbuck SG, Eisenhauer EA et al: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000, 92, 205-216.
  31. Eichenberger T, Trachtenberg J, Toor P et al: Ketoconazole: a possible direct cytotoxic effect on prostate carcinoma cells. J Urol 1989, 141, 190-191.
  32. Small EJ, Baron A, Bok R: Simultaneous antiandrogen withdrawal and treatment with ketoconazole and hydrocortisone in patients with advanced prostate carcinoma. Cancer 1997, 80, 1755-1759.
  33. Harris KA, Weinberg V, Bok RA et al: Low dose ketoconazole with replacement doses of hydrocortisone in patients with progressive androgen independent prostate cancer. J Urol 2002, 168, 542-545.
  34. Haynes RC: Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors or the synthesis and actions of adrenocortical hormones. Gillman AG RTNATP, editor. Goodman and Gilman´s The Pharmacological Basis of Therapeutics, 1458. 1990. New York, Pergamom Press.
  35. Abratt RP, Brune D, Dimopoulos MA et al: Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer. Ann Oncol 2004, 15, 1613-1621.
  36. Fakih M, Johnson CS, Trump DL: Glucocorticoids and treatment of prostate cancer: a preclinical and clinical review. Urology 2002, 60, 553-561.
  37. Fossa SD, Slee PH, Brausi M et al: Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy: a phase III study of the European organization for research and treatment of cancer genitourinary group. J Clin Oncol 2002, 19, 62-71.
  38. Small EJ, Meyer M, Marshall ME et al: Suramin therapy for patients with symptomatic hormone-refractory prostate cancer: results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone. J Clin Oncol 2000, 18, 1440-1450.
  39. Kantoff PW, Halabi S, Conaway M et al: 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 1999, 17, 2506-2513.
  40. Landstrom M, Damber JE, Bergh A: Estrogen treatment postpones the castration-induced dedifferentiation of Dunning R3327-PAP prostatic adenocarcinoma. Prostate 1994, 25, 10-18.
  41. de Voogt HJ, Smith PH, Pavone-Macaluso M et al: 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 1986, 135, 303-307.
  42. Small EJ, Frohlich MW, Bok R et al: Prospective trial of the herbal supplement PC-SPES in patients with progressive prostate cancer. J Clin Oncol 2000, 18, 3595-3603.
  43. Weinrobe MC, Montgomery B: Acquired bleeding diathesis in a patient taking PC-SPES. N Engl J Med 2001, 345, 1213-1214.
  44. Yagoda A, Petrylak D: Cytotoxic chemotherapy for advanced hormone-resistant prostate cancer. Cancer 1993, 71 (3 Suppl), 1098-1109.
  45. Fossa SD, Aaronson NK, Newling D et al: Quality of life and treatment of hormone resistant metastatic prostatic cancer. The EORTC Genito-Urinary Group. Eur J Cancer 1990, 26, 1133-1136.
  46. Hudes G, Einhorn L, Ross E et al: Vinblastine versus vinblastine plus oral estramustine phosphate for patients with hormone-refractory prostate cancer: A Hoosier Oncology Group and Fox Chase Network phase III trial. J Clin Oncol 1999, 17, 3160-3166.
  47. Albrecht W, Van Poppel H, Horenblas S et al: Randomized Phase II trial assessing estramustine and vinblastine combination chemotherapy vs estramustine alone in patients with progressive hormone-escaped metastatic prostate cancer. Br J Cancer 2004, 90, 100-105.
  48. Tannock IF, Osoba D, Stockler MR et al: 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 1996, 14, 1756-1764.
  49. Kantoff PW, Halabi S, Conaway M et al: 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 1999, 17, 2506-2513.
  50. Petrylak DP, Tangen CM, Hussain MH et al: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004, 351, 1513-1520.
  51. Budman DR, Calabro A: Zoledronic acid (Zometa) enhances the cytotoxic effect of gemcitabine and fluvastatin: in vitro isobologram studies with conventional and nonconventional cytotoxic agents. Oncology 2006, 70, 147-153.
  52. Ullen A, Lennartsson L, Harmenberg U et al: Additive/synergistic antitumoral effects on prostate cancer cells in vitro following treatment with a combination of docetaxel and zoledronic acid. Acta Oncol 2005, 44, 644-650.
  53. Stephenson AJ, Scardino PT, Eastham JA et al: Postoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Clin Oncol 2005, 23, 7005-7012.
  54. D´Amato RJ, Loughnan MS, Flynn E, Folkman J: Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994, 91, 4082-4085.
  55. Figg WD, Dahut W, Duray P et al: A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer. Clin Cancer Res 2001, 7, 1888-1893.
  56. Dahut WL, Gulley JL, Arlen PM et al: Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer. J Clin Oncol 2004, 22, 2532-2539.
  57. Picus J, Halabi S, Rini B et al: The use of bevacizumab (B) with docetazel (D) and estramustine (E) in hormone refractory prostate cancer (HRPC): initial results of CALGB 90006. Proc Am Soc Clinical Oncol 2003, 22, 1578.
  58. Beer TM, Eilers KM, Garzotto M et al: Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer. J Clin Oncol 2003, 21, 123-128.
  59. Beer TM, Ryan CW, Venner PM JD et al: Interim results from ASCENT: a double-blinded randomized study of DN-101 (high dose calcitriol) plus docetaxel vs. placebo plus docetaxel in androgen-independent prostate cancer (AIPC). Proc Am Soc Clinical Oncol 2005, 23, 4516.
  60. Nelson JB, Hedican SP, George DJ et al: Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med 1995, 1, 944-949.
  61. Nelson JB, Nguyen SH, Wu-Wong JR et al: New bone formation in an osteoblastic tumor model is increased by endothelin-1 overexpression and decreased by endothelin A receptor blockade. Urology 1999, 53, 1063-1069.
  62. Yin JJ, Mohammad KS, Kakonen SM et al: A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proc Natl Acad Sci USA 2003, 100, 10954-10959.
  63. Nelson JB, Nabulsi AA, Vogelzang NJ et al: Suppression of prostate cancer induced bone remodeling by the endothelin receptor A antagonist atrasentan. J Urol 2003, 169, 1143-1149.
  64. Vogelzang NJ, Nelson JB, Schulman CC et al: Meta-analysis of clinical trials of atrasentan 10 mg in metastatic hormone-refractory prostate cancer. Proc Am Soc Clinical Oncol 2005, 23, 4563.
  65. Kibel AS NJ. Campbell´s urology, 8th ed Molecular genetics and cancer biology, in Walsh PC (Ed), 2625-2671. 2002. Philadelphia, Saunders.
  66. Canil CM, Moore MJ, Winquist E et al: Randomized phase II study of two doses of gefitinib in hormone-refractory prostate cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group. J Clin Oncol 2005, 23, 455-460.
  67. Ziada A, Barqawi A, Glode LM et al: The use of trastuzumab in the treatment of hormone refractory prostate cancer; phase II trial. Prostate 2004, 60, 332-337.
  68. Rao K, Goodin S, Levitt MJ et al: A phase II trial of imatinib mesylate in patients with prostate specific antigen progression after local therapy for prostate cancer. Prostate 2005, 62, 115-122.
  69. Ioffe ML, White E, Nelson DA et al: Epothilone induced cytotoxicity is dependent on p53 status in prostate cells. Prostate 2004, 61, 243-247.
  70. Hussain M, Tangen CM, Lara PN et al: Ixabepilone (epothilone B analogue BMS-247550) is active in chemotherapy-naive patients with hormone-refractory prostate cancer: a Southwest Oncology Group trial S0111. J Clin Oncol 2005, 23, 8724-8729.
  71. Galsky MD, Small EJ, Oh WK et al: Multi-institutional randomized phase II trial of the epothilone B analog ixabepilone (BMS-247550) with or without estramustine phosphate in patients with progressive castrate metastatic prostate cancer. J Clin Oncol 2005, 23, 1439-1446.
  72. Rosenberg JE, Galsky MD, Weinberg V et al: Response to second-line taxane-based therapy after first-line epothilone B analogue BMS-247550 (BMS) therapy in hormone-refractory prostate cancer (HRPC). Proc Am Soc Clinical Oncol 2004, 22, 4564.
  73. Lin AM, Rosenberg JE, Weinberg VK et al: Clinical outcome of taxane-resistant (TR) hormone refractory prostate cancer (HRPC) patients (pts) treated with subsequent chemotherapy (ixabepilone) (Ix) or mitoxantrone/prednisone. Proc Am Soc Clinical Oncol 2006, 24, 4558.
  74. Sternberg CN, Whelan P, Hetherington J et al: Phase III trial of satraplatin, an oral platinum plus prednisone vs. prednisone alone in patients with hormone-refractory prostate cancer. Oncology 2005, 68, 2-9.
  75. Iversen PL, Arora V, Acker AJ et al: Efficacy of antisense morpholino oligomer targeted to c-myc in prostate cancer xenograft murine model and a Phase I safety study in humans. Clin Cancer Res 2003, 9, 2510-2519.
  76. Chi KN: Targeting Bcl-2 with oblimersen for patients with hormone refractory prostate cancer. World J Urol 2005, 23, 33-37.
  77. Tolcher AW, Chi K, Kuhn J et al: A phase II, pharmacokinetic, and biological correlative study of oblimersen sodium and docetaxel in patients with hormone-refractory prostate cancer. Clin Cancer Res 2005, 11, 3854-3861.
  78. Vile RG, Russell SJ, Lemoine NR: Cancer gene therapy: hard lessons and new courses. Gene Ther 2000, 7, 2-8.
  79. Foley R, Lawler M, Hollywood D: Gene-based therapy in prostate cancer. Lancet Oncol 2004, 5, 469-479.
  80. Xu J, Kalos M, Stolk JA et al: Identification and characterization of prostein, a novel prostate-specific protein. Cancer Res 2001, 61, 1563-1568.
  81. Valone FH SEMM: Dendritic-based treatment of cancer: closing in on a cellular therapy. Cancer J 2001, 7 (suppl 2), 53-61.
  82. Higano CS, Burch PA, Small EJ et al: Immunotherapy (APC8015) forAndrogen Independent Prostate Cancer: Final Progression and Survival Data from a Second Phase 3 Trial, 9902, ECCO, abstract PS1, 2005.
  83. Small E, Higano C, Smith D et al: A phase II study of an allogeneic GM-CSF gene-transduced prostate cancer cell line vaccine in patients with metastatic hormone-refractory prostate cancer (HRPC). Proc Am Soc Clinical Oncol 2004, 22, 4565.
  84. Smith MR, Nelson JB: Future therapies in hormone-refractory prostate cancer. Urology 2005, 65 (Suppl), 9-16.
  85. Saad F, Gleason DM, Murray R L et al: A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002, 94, 1458-1468.
  86. Small EJ, Smith MR, Seaman JJ et al: Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer. J Clin Oncol 2003, 21, 4277-4284.
  87. Ernst DS, Tannock IF, Winquist EW et al: Randomized, double-blind, controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone and placebo in patients with hormone-refractory prostate cancer and pain. J Clin Oncol 2003, 21, 3335-3342.
  88. Tosi P, Zamagni E, Cangini D et al: Osteonecrosis of the jaws in newly diagnosed multiple myeloma patients treated with zoledronic acid and thalidomide-dexamethasone. Blood 2006, 108, 3951-3952.
  89. Arrigo AP, Tanaka K, Goldberg AL, Welch WJ: Identity of the 19S `prosome´ particle with the large multifunctional protease complex of mammalian cells (the proteasome). Nature 1988, 331, 192-194.
  90. Papandreou CN, Daliani DD, Nix D et al: Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer. J Clin Oncol 2004, 22, 2108-2121.
  91. Lapointe J, Li C, Higgins JP et al: Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA 2004, 101, 811-816.
  92. Singh D, Febbo PG, Ross K et al: Gene expression correlates of clinical prostate cancer behavior. Cancer Cell 2002, 1, 203-209.
  93. Bettuzzi S, Scaltriti M, Caporali A et al: Successful prediction of prostate cancer recurrence by gene profiling in combination with clinical data: a 5-year follow-up study. Cancer Res 2003, 63, 3469-3472.

correspondence

Theo M. de Reijke
Department of Urology
Academic Medical Center
Meibergdreef 9
1105 AZ AMSTERDAM
T.M.deReyke@amc.uva.nl
tel. +31 20 5666004