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The changing pattern of management for hormone-refractory, metastatic prostate cancer

Abstract

Prostate cancer responds initially to hormonal manipulation by androgen withdrawal and peripheral androgen blockade. The inevitable progression to a hormone-refractory state is accompanied by an exacerbation of local symptoms and metastatic spread, principally to the bones, which has a considerable impact on quality of life and survival. Treatment of hormone-refractory prostate cancer is palliative, and surgery and radiotherapy are used for the relief of lower urinary tract symptoms and localized painful bony metastases. Systemic treatments are not widely accepted in this setting, but clinical trials have demonstrated the potential for bone targeting agents such as strontium-89 and the bisphosphonates to palliate painful bone metastases and to delay progression in certain settings. Chemotherapy with mitozantrone in combination with steroids has previously been shown to have palliative benefits and to delay progression. The additional costs incurred by the use of chemotherapy or bone-targeting therapies may be offset by gains in overall care with fewer in-patient admissions compared with steroid monotherapy . Recent clinical trials have demonstrated that docetaxel significantly improves patient quality of life, and importantly, increases survival. Future studies investigating the timing of chemotherapy, combinations with existing treatments or other novel therapies are underway.

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References

  1. Parkin DM, Bray F, Ferlay J, Pisani P . Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001; 94: 153–156.

    Article  CAS  Google Scholar 

  2. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Prostate Cancer Trialists' Collaborative Group. [comment]. Lancet 2000; 355: 1491–1498.

  3. Crawford ED, Blumenstein BA, Goodman PJ, Davis MA, Eisenberger MA, McLeod DG et al. Leuprolide with and without flutamide in advanced prostate cancer. Cancer 1990; 66: 1039–1044.

    Article  CAS  Google Scholar 

  4. Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ et al. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med 1998; 339: 1036–1042.

    Article  CAS  Google Scholar 

  5. Robertson CN, Roberson KM, Padilla GM, O'Brien ET, Cook JM, Kim CS et al. Induction of apoptosis by diethylstilbestrol in hormone-insensitive prostate cancer cells. J Natl Cancer Inst 1996; 88: 908–917.

    Article  CAS  Google Scholar 

  6. Crawford ED, Blumenstein BA, Goodman PJ, Davis MA, Eisenberger MA, McLeod DG et al. Leuprolide with and without flutamide in advanced prostate cancer. Cancer 1990; 66: 1039–1044.

    Article  CAS  Google Scholar 

  7. Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ et al. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med 1998; 339: 1036–1042.

    Article  CAS  Google Scholar 

  8. Denis LJ, Keuppens F, Smith PH, Whelan P, de Moura JL, Newling D et al. Maximal androgen blockade: final analysis of EORTC phase III trial 30853. EORTC Genito-Urinary Tract Cancer Cooperative Group and the EORTC Data Center. Eur Urol 1998; 33: 144–151.

    Article  CAS  Google Scholar 

  9. Fossa SD, Slee PH, Brausi M, Horenblas S, Hall RR, Hetherington JW 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 2001; 19: 62–71.

    Article  CAS  Google Scholar 

  10. Yagoda A, Petrylak D . Cytotoxic chemotherapy for advanced hormone-resistant prostate cancer. Cancer 1993; 71: 1098–1109.

    Article  CAS  Google Scholar 

  11. Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points [see comments]. J Clin Oncol 1996; 14: 1756–1764.

    Article  CAS  Google Scholar 

  12. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004; 351: 1502–1512.

    Article  CAS  Google Scholar 

  13. Petrylak DP, Tangen CM, Hussain MH, Lara PN, Jr, Jones JA et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004; 351: 1513–1520.

    Article  CAS  Google Scholar 

  14. Stewart AJ, Scher HI, Chen MH, McLeod DG, Carroll PR, Moul JW et al. Prostate-specific antigen nadir and cancer-specific mortality following hormonal therapy for prostate-specific antigen failure. J Clin Oncol 2005; 23: 6556–6560.

    Article  Google Scholar 

  15. Slovin SF, Wilton AS, Heller G, Scher HI . Time to detectable metastatic disease in patients with rising prostate-specific antigen values following surgery or radiation therapy. Clin Cancer Res 2005; 11: 8669–8673.

    Article  CAS  Google Scholar 

  16. Loberg RD, Fielhauer JR, Pienta BA, Dresden S, Christmas P, Kalikin LM et al. Prostate-specific antigen doubling time and survival in patients with advanced metastatic prostate cancer. [Review] [17 refs]. Urology 2003; 62 (Suppl 1): 128–133.

    Article  Google Scholar 

  17. Lee AK, D'Amico AV . Utility of prostate-specific antigen kinetics in addition to clinical factors in the selection of patients for salvage local therapy. [Review] [21 refs]. J Clin Oncol 2005; 23: 8192–8197.

    Article  Google Scholar 

  18. Lee AK, Levy LB, Cheung R, Kuban D . Prostate-specific antigen doubling time predicts clinical outcome and survival in prostate cancer patients treated with combined radiation and hormone therapy. Int J Radiat Oncol Biol Phy 2005; 63: 456–462.

    Article  Google Scholar 

  19. Diamond TH, Bucci J, Kersley JH, Aslan P, Lynch WB, Bryant C . Osteoporosis and spinal fractures in men with prostate cancer: risk factors and effects of androgen deprivation therapy. J Urol 2004; 172: 529–532.

    Article  CAS  Google Scholar 

  20. Huddart RA, Rajan B, Law M, Meyer L, Dearnaley DP . Spinal cord compression in prostate cancer: treatment outcome and prognostic factors. Radiother Oncol 1997; 44: 229–236.

    Article  CAS  Google Scholar 

  21. Cereceda LE, Flechon A, Droz JP . Management of vertebral metastases in prostate cancer: a retrospective analysis in 119 patients. Clin Prostate Cancer 2003; 2: 34–40.

    Article  Google Scholar 

  22. Oefelein MG . Prognostic significance of obstructive uropathy in advanced prostate cancer. Urology 2004; 63: 1117–1121.

    Article  Google Scholar 

  23. Crain DS, Amling CL, Kane CJ . Palliative transurethral prostate resection for bladder outlet obstruction in patients with locally advanced prostate cancer. J Urol 2004; 171: 668–671.

    Article  Google Scholar 

  24. Perez CA, Cosmatos D, Garcia DM, Eisbruch A, Poulter CA . Irradiation in relapsing carcinoma of the prostate. Cancer 1993; 71: 1110–1122.

    Article  CAS  Google Scholar 

  25. Wilson JR, Urwin GH, Stower MJ . The role of percutaneous nephrostomy in malignant ureteric obstruction. Ann R Coll Surg Engl 2005; 87: 21–24.

    Article  CAS  Google Scholar 

  26. Kynaston HG, Keen CW, Matthews PN . Radiotherapy for palliation of locally advanced prostatic carcinoma. Br J Urol 1990; 66: 515–517.

    Article  CAS  Google Scholar 

  27. Cleare AJ Miell J, Heap E, Sookdeo S, Young L, Malhi GS, O'Keane V . Hypothalamo–pituitary–adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy. J Clin Endocrinol Metab 2001; 86: 3545–3554.

    Article  Google Scholar 

  28. Plowman PN, Perry LA, Chard T . Androgen suppression by hydrocortisone without aminoglutethimide in orchiectomised men with prostatic cancer. Br J Urol 1987; 59: 255–257.

    Article  CAS  Google Scholar 

  29. Fossa SD, Slee PH, Brausi M, Horenblas S, Hall RR, Hetherington JW 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 2001; 19: 62–71.

    Article  CAS  Google Scholar 

  30. Price P, Hoskin PJ, Easton D, Austin D, Palmer SG, Yarnold JR . Prospective randomised trial of single and multifraction radiotherapy schedules in the treatment of painful bony metastases. Radiother Oncol 1986; 6: 247–255.

    Article  CAS  Google Scholar 

  31. Hoskin PJ, Price P, Easton D, Regan J, Austin D, Palmer S et al. A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain. Radiother Oncol 1992; 23: 74–78.

    Article  CAS  Google Scholar 

  32. Quilty PM, Kirk D, Bolger JJ, Dearnaley DP, Lewington VJ, Mason MD et al. A comparison of the palliative effects of strontium-89 and external-beam radiotherapy in metastatic prostate cancer. Radiother Oncol 1994; 31: 33–40.

    Article  CAS  Google Scholar 

  33. Bolger JJ, Dearnaley DP, Kirk D, Lewington VJ, Mason MD, Quilty PM et al. Strontium-89 (Metastron) versus external-beam radiotherapy in patients with painful bone metastases secondary to prostatic cancer: preliminary report of a multicenter trial. UK Metastron Investigators Group. Semin Oncol 1993; 20: 32–33.

    CAS  PubMed  Google Scholar 

  34. Porter AT, McEwan AJ . Strontium-89 as an adjuvant to external-beam radiation improves pain relief and delays disease progression in advanced prostate cancer: results of a randomized controlled trial. Semin Oncol 1993; 20: 38–43.

    CAS  PubMed  Google Scholar 

  35. Oosterhof GO, Roberts JT, de Reijke TM, Engelholm SA, Horenblas S, von der Maase H et al. Strontium(89) chloride versus palliative local field radiotherapy in patients with hormonal escaped prostate cancer: a phase III study of the European Organisation for Research and Treatment of Cancer, Genitourinary Group. Eur Urol 2003; 44: 519–526.

    Article  CAS  Google Scholar 

  36. Dafermou A, Colamussi P, Giganti M, Cittanti C, Bestagno M, Piffanelli A . A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer. Eur J Nucl Med 2001; 28: 788–798.

    Article  CAS  Google Scholar 

  37. Kraeber-Bodere F, Campion L, Rousseau C, Bourdin S, Chatal JF, Resche I . Treatment of bone metastases of prostate cancer with strontium-89 chloride: efficacy in relation to the degree of bone involvement. Eur J Nucl Med 2000; 27: 1487–1493.

    Article  CAS  Google Scholar 

  38. Coleman RE . Bisphosphonates in breast cancer. Ann Oncol 2005; 16: 687–695.

    Article  CAS  Google Scholar 

  39. Green JR . Preclinical pharmacology of zoledronic acid. [Review] [51 refs]. Semin Oncol 2002; 29: 3–11.

    Article  CAS  Google Scholar 

  40. Lipton A, Glover D, Harvey H, Grabelsky S, Zelenakas K, Macerata R et al. Pamidronate in the treatment of bone metastases: results of 2 dose-ranging trials in patients with breast or prostate cancer. Ann Oncol 1994; 5 (Suppl 7): S31–S35.

    PubMed  Google Scholar 

  41. Small EJ, Smith MR, Seaman JJ, Petrone S, Kowalski MO . 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.

    Article  CAS  Google Scholar 

  42. Dearnaley DP, Sydes MR, Mason MD, Stott M, Powell CS, Robinson AC et al. A double-blind, placebo-controlled, randomized trial of oral sodium clodronate for metastatic prostate cancer (MRC PR05 Trial). J Natl Cancer Inst 2003; 95: 1300–1311.

    Article  CAS  Google Scholar 

  43. Mason M . Development of bone metastases from prostate cancer: first results of the MRC PR04 trial (ISCRTN 61384873). Proc Am Soc Clin Oncol 2004; (abstract 4511).

  44. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. [comment]. J Natl Cancer Inst 2002; 94: 1458–1468.

    Article  CAS  Google Scholar 

  45. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004; 96: 879–882.

    Article  CAS  Google Scholar 

  46. Patchell R, Tibbs PA, Regine WF, Payne R, Saris S, Kryscio RJ et al. A randomized trial of direct decompressive surgical resection in the treatment of spinal cord compression caused by metastasis. Proc Am Soc Clin Oncol 2003; 22: 1.

    Google Scholar 

  47. Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V et al. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. [comment]. J Clin Oncol 1999; 17: 2506–2513.

    Article  CAS  Google Scholar 

  48. Dowling AJ, Panzarella T, Ernst DS, Neville AJ, Moore MJ, Tannock IF . A retrospective analysis of the relationship between changes in serum PSA, palliative response and survival following systemic treatment in a Canadian randomized trial for symptomatic hormone-refractory prostate cancer. Ann Oncol 2001; 12: 773–778.

    Article  CAS  Google Scholar 

  49. Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V et al. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study.[comment]. J Clin Oncol 1999; 17: 2506–2513.

    Article  CAS  Google Scholar 

  50. Berry W, Dakhil S, Modiano M, Gregurich M, Asmar L . Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone-refractory prostate cancer. J Urol 2002; 168: 2439–2443.

    Article  CAS  Google Scholar 

  51. Bloomfield DJ, Krahn MD, Neogi T, Panzarella T, Smith TJ, Warde P et al. Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points. J Clin Oncol 1998; 16: 2272–2279.

    Article  CAS  Google Scholar 

  52. Berry WR, Hathorn JW, Dakhil SR, Loesch DM, Jackson DV, Gregurich MA et al. Phase II randomized trial of weekly paclitaxel with or without estramustine phosphate in progressive, metastatic, hormone-refractory prostate cancer. Clin Prostate Cancer 2004; 3: 104–111.

    Article  CAS  Google Scholar 

  53. McEwan AJ, Amyotte GA, McGowan DG, MacGillivray JA, Porter AT . A retrospective analysis of the cost effectiveness of treatment with Metastron in patients with prostate cancer metastatic to bone. Eur Urol 1994; 26 (Suppl 1): 26–31.

    Article  Google Scholar 

  54. Oudard S, Legrier ME, Boye K, Bras-Goncalves R, de Pinieux G, De Cremoux P et al. Activity of docetaxel with or without estramustine phosphate versus mitoxantrone in androgen dependent and independent human prostate cancer xenografts. J Urol 2003; 169: 1729–1734.

    Article  CAS  Google Scholar 

  55. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004; 351: 1502–1512.

    Article  CAS  Google Scholar 

  56. Petrylak DP, Tangen CM, Hussain MH, Lara Jr PN, Jones JA, Taplin ME et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004; 351: 1513–1520.

    Article  CAS  Google Scholar 

  57. Abratt RP, Brune D, Dimopoulos MA, Kliment J, Breza J, Selvaggi FP 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.

    Article  CAS  Google Scholar 

  58. Sternberg CN . Satraplatin in the treatment of hormone-refractory prostate cancer. Br J Urol Int 2005; 96: 990–994.

    Article  CAS  Google Scholar 

  59. Sternberg CN, Whelan P, Hetherington J, Paluchowska B, Slee PH, Vekemans K 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.

    Article  CAS  Google Scholar 

  60. Ziada A, Barqawi A, Glode LM, Varella-Garcia M, Crighton F, Majeski S et al. The use of trastuzumab in the treatment of hormone-refractory prostate cancer; phase II trial. Prostate 2004; 60: 332–337.

    Article  CAS  Google Scholar 

  61. Nelson J, Bagnato A, Battistini B, Nisen P, Norman P, Carducci MA et al. The endothelin axis: emerging role in cancer. [Review] [73 refs]. Nat Rev 2003; (Cancer 3): 110–116.

    Article  Google Scholar 

  62. Nelson JB, Nabulsi AA, Vogelzang NJ, Breul J, Zonnenberg BA, Daliani DD et al. Suppression of prostate cancer induced bone remodeling by the endothelin receptor A antagonist atrasentan. J Urol 2003; 169: 1143–1149.

    Article  CAS  Google Scholar 

  63. Carducci MA, Padley RJ, Breul J, Vogelzang NJ, Zonnenberg BA, Daliani DD et al. Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: a randomized, phase II, placebo-controlled trial. J Clin Oncol 2003; 21: 679–689.

    Article  CAS  Google Scholar 

  64. Vordos D, Paule B, Vacherot F, Allory Y, Salomon L, Hoznek A et al. Docetaxel and zoledronic acid in patients with metastatic hormone-refractory prostate cancer. BJU Int 2004; 94: 524–527.

    Article  CAS  Google Scholar 

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James, N., Bloomfield, D. & Luscombe, C. The changing pattern of management for hormone-refractory, metastatic prostate cancer. Prostate Cancer Prostatic Dis 9, 221–229 (2006). https://doi.org/10.1038/sj.pcan.4500880

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