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Updates on therapeutic targets and agents in castrate-resistant prostate cancer


Authors: M. O. Bishr;  J.-B. Lattouf;  P. O. Gannon;  F. Saad
Authors place of work: University of Montreal Hospital Center, 1560 Sherbrooke east, Montreal, Canada
Published in the journal: Urol List 2012; 10(2): 15-23

Summary

Prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer in men and the second to third most common cause of cancer death in the western world. Nearly all patients with metastatic disease will eventually experience disease progression despite castration with a median duration of response of 18–24 months; development of castration-resistant prostate cancer (CRPC) is only a matter of time. CRPC is defined by disease progression despite androgen-deprivation therapy. CRPC presents a spectrum of disease ranging from rising PSA levels to metastases and significant debilitation from cancer symptoms. Prognosis is associated with se­ve­ral factors, including performance status, presence of bone pain, extent of disease on bone scan, and serum levels of alkaline phosphatase. Based on our enhanced understanding of tumor biology, including the role of tumor, host, and hormonal signaling, there has been rational development of new therapies for CRPC. Over the last decade, several clinical trials have been launched to study novel agents targeting different mechanisms of PCa progression that has been culminated by success of four new agents for CRPC (cabazitaxel, sipuleucel-T, denosumab, and abiraterone acetate) and several more molecules are on the horizon. The purpose of this review is to discuss the new therapeutic targets in CRPC focusing on new promising agents.

Key words:
prostate cancer, castrate-resistance prostate cancer, bone metastasis, androgen receptor, chemotherapy, immunotherapy, angiogenesis


Zdroje

1. Jemal A, Siegel R, Ward E et al. Cancer statistics, 2008. CA: Cancer J Clin 2008; 58(2): 71–96.

2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer V.2. 2009. Available at: http://www.nccn.org/ professionals/physician_gls/f_guidelines.asp. Accessed April 2011.

3. Sharifi N, Dahut WL, Steinberg SM et al. A retrospective study of the time to clinical endpoints for advanced prostate cancer. BJU Int 2005; 96(7): 985–989.

4. Hotte SJ, Saad F. Current management of castrate-resistant prostate cancer. Current oncology 2010; 17 (Suppl 2): S72–79.

5. Mohler JL, Gregory CW, Ford OH 3rd et al. The androgen axis in recurrent prostate cancer. Clin Cancer Res 2004; 10(2): 440–448.

6. Mostaghel EA, Page ST, Lin DW et al. Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res 2007; 67(10): 5033–5041.

7. 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 2001; 19(1): 62–71.

8. Knudsen KE, Scher HI. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res 2009; 15(15): 4792–4798.

9. 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(6): 1756–1764.

10. 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(8): 2506–2513.

11. 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(15): 1513–1520.

12. 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(15): 1502–1512.

13. Winquist E, Waldron T, Berry S et al. Non-hormo­nal systemic therapy in men with hormone-refractory prostate cancer and metastases: a systematic review from the Cancer Care Ontario Program in Evidence-based Care's Genitourinary Cancer Disease Site Group. BMC Cancer 2006; 6: 112.

14. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. Available at: www.nccn.org/profes­sionals//physician_gls/PDF/prostate.pdf Accessed April 2011.

15. Loriot Y, Massard C, Gross-Goupil M et al. The inter­val from the last cycle of docetaxel-based chemotherapy to progression is associated with the efficacy of subsequent docetaxel in patients with prostate cancer. Eur J Cancer 2010; 46(10): 1770–1772.

16. de Bono JS, Oudard S, Ozguroglu M et al. Pred­nisone plus cabazitaxel or mitoxantrone for metasta­tic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010; 376(9794): 1147–1154.

17. 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(7): 1439–1446.

18. Rosenberg JE, Galsky MD, Rohs NC et al. A retrospective evaluation of second-line chemotherapy response in hormone-refractory prostate carcinoma: second line taxane-based therapy after first-line epothilone-B analog ixabepilone (BMS-247550) therapy. Cancer 2006; 106(1): 58–62.

19. Small E, Harzstark A, Weinberg VK et al. Ixabe­pilo­ne, mitoxantrone, and prednisone in patients with metasta­tic castration-resistant prostate cancer refractory to do­ce­taxel-based therapy: A phase II study of the DOD Prostate Cancer Clinical Trials Consortium. J Clin Oncol 2009; 27.

20. Beardsley EK, Saad F, Eigl B et al. A phase II study of patupilone in patients (pts) with metastatic castration- resistant prostate cancer (CRPC) who have progressed after docetaxel. J Clin Oncol 2009; 27.

21. Chi KN, Beardsley EK, Venner PM et al. A phase II study of patupilone in patients with metastatic hormone refractory prostate cancer (HRPC) who have progressed after docetaxel. J Clin Oncol 2008; 26.

22. Tetu B, Ro JY, Ayala AG et al. Small cell carcinoma of the prostate. Part I. A clinicopathologic study of 20 cases. Cancer 1987; 59(10): 1803–1809.

23. Sternberg CN, Petrylak DP, Sartor O et al. Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. J Clin Oncol 2009; 27(32): 5431–5438.

24. Zhu W, Zhu DS, Madan RA et al. Treatment of castration-resistant prostate cancer: updates on therapeutics targeting the androgen receptor signaling pathway. Am J Ther 2010; 17(2): 176–181.

25. Sciarra A, Cardi A, Di Silverio F. Antiandrogen monotherapy: recommendations for the treatment of prostate cancer. Urol Int 2004; 72(2): 91–98.

26. Cox RL, Crawford ED. Estrogens in the treatment of prostate cancer. J Urol 1995; 154(6): 1991–1998.

27. Potter GA, Barrie SE, Jarman M et al. Novel steroidal inhibitors of human cytochrome P45017 alpha (17 alpha-hydroxylase-C17,20-lyase): potential agents for the treatment of prostatic cancer. J Med Chem 1995; 38(13): 2463–2471.

28. Barrie SE, Potter GA, Goddard PM et al. Pharma­cology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase). J Steroid Biochem Mol Biol 1994; 50(5–6): 267–273.

29. Attard G, Reid AH, A'Hern R et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol 2009; 27(23): 3742–3748.

30. Danila DC, Morris MJ, de Bono JS et al. Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. J Clin Oncol 2010; 28(9): 1496–1501.

31. Ryan CJ, Smith MR, Fong L et al. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate de­mon­strating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J Clin Oncol 2010; 28(9): 1481–1488.

32. Saad F, de Bono JS, Haqq CM et al. Abiraterone acetate plus low-dose prednisone has a favorable safety profile, improves survival and produces PSA and radiographic responses in metastatic castration--resistant prostate cancer progressing after docetaxe­­­l--based chemotherapy: results from COU-AA-301, a randomized, double-blind, placebo-controlled, phase III study. J Urol 2011;1 85: e283.

33. Dreicer R, Agus DB, MacVicar GR et al. Safety, phar­macokinetics, and efficacy of TAK-700 in meta­static castration-resistant prostrate cancer: A phase I/II, open-label study. J Clin Oncol 2010; 28: abstract 3084.

34. Tran C, Ouk S, Clegg NJ et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 2009; 324(5928): 787–790.

35. Scher HI, Beer TM, Higano CS et al. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet 2010; 375(9724): 1437–1446.

36. George DJ, Halabi S, Shepard TF et al. Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B 9480. Clin Cancer Res 2001; 7(7): 1932–1936.

37. Melnyk O, Zimmerman M, Kim KJ et al. Neutra­lizing anti-vascular endothelial growth factor antibody inhibits further growth of established prostate cancer and metastases in a pre-clinical model. J Urol 1999; 161(3): 960–963.

38. Picus J, Halabi S, Kelly WK et al. A phase 2 study of estramustine, docetaxel, and bevacizumab in men with castrate-resistant prostate cancer: results from Cancer and Leukemia Group B Study 90006. Cancer 2011; 117(3): 526–533.

39. Kelly WK, Halabi S, Carducci MA et al. A rando­mized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castration-resistant prostate cancer (mCRPC): Survival results of CALGB 90401. J Clin Oncol 2010; 28: abstract LBA4511.

40. Verheul HM, Hammers H, van Erp K et al. Vascular endothelial growth factor trap blocks tumor growth, metastasis formation, and vascular leakage in an ortho­topic murine renal cell cancer model. Clin Cancer Res 2007; 13(14): 4201–4208.

41. Isambert N, Freyer G, Zanetta S et al. A phase I dose escalation and pharmacokinetic (PK) study of intravenous aflibercept (VEGF trap) plus docetaxel (D) in patients (pts) with advanced solid tumors: Preliminary results. J Clin Oncol 2008; 26: abstract 3599.

42. Motzer RJ, Hutson TE, Tomczak P et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007; 356(2): 115–124.

43. Sonpavde G, Periman PO, Bernold D et al. Sunitinib malate for metastatic castration-resistant prostate cancer following docetaxel-based chemo­therapy. Annals of oncology 2010; 21(2): 319–324.

44. 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(13): 2532–2539.

45. Petrylak DP, Resto-Garces K, Tibyan M et al. A phase I open-label study using lenalidomide and docetaxel in castration- resistant prostate cancer. J Clin Oncol 2009; 27, 15s.

46. Pili R, Haggman M, Stadler WM et al. A rando­mized, multicenter, international phase II study of tasquinimod in chemotherapy naďve patients with metastatic castrate-resistant prostate cancer (CRPC). J Clin Oncol 2010; 28.

47. Small EJ, Fratesi P, Reese DM et al. Immun­o­therapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol 2000; 18(23): 3894–3903.

48. Kantoff PW, Higano CS, Shore ND et al. Sipuleu­cel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363(5): 411–422.

49. Small EJ, Schellhammer PF, Higano CS et al. Pla­cebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 2006; 24(19): 3089–3094.

50. Higano CS, Schellhammer PF, Small EJ et al. Inte­grated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer 2009; 115(16): 3670–3679.

51. Madan RA, Arlen PM, Mohebtash M et al. Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer. Expert Opin Investig Drugs 2009; 18(7): 1001–1011.

52. Kantoff PW, Schuetz TJ, Blumenstein BA et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immu­no­therapy in metastatic castration-resistant prostate cancer. J Clin Oncol 2010; 28(7): 1099–1105.

53. Antonarakis ES, Carducci MA, Eisenberger MA. Novel targeted therapeutics for metastatic castration-resistant prostate cancer. Cancer Lett 2010; 291(1): 1–13.

54. Small EJ, Sacks N, Nemunaitis J et al. Granulocyte macrophage colony-stimulating factor--secreting allogeneic cellular immunotherapy for hormone-refrac­tory prostate cancer. Clin Cancer Res 2007; 13(13): 3883–3891.

55. Higano CS, Corman JM, Smith DC et al. Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer. Cancer 2008; 113(5): 975–984.

56. Small E, Demkow T, Gerritsen WR et al. A phase III trial of GVAX immunotherapy for prostate cancer in combination with docetaxel versus docetaxel plus prednisone in symptomatic, castration-resistant prostate cancer (CRPC). Available at: http://www. asco.org/ ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=64&abstractID=20295 2009; Abstract #7.

57. Cell Genesys Inc: Cell Genesys Halts VITAL-2 GVAX Trial in Advanced Prostate Cancer. Available at: http://www.drugs.com/news/cell-genesys-halts-vital-2-gvax-trial-advanced-prostate-cancer-13371.html16, 2008.

58. Chambers CA, Kuhns MS, Egen JG et al. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol 2001; 19: 565–594.

59. Tollefson MK, Karnes RJ, Thompson RH et al. A randomized phase II study of ipilimumab with androgen ablation compared with androgen ablation alone in patients with advanced prostate cancer. Available at: http://www.asco.org/ascov2/Meetings/ Abstracts?&vmview=abst_detail_view&confID=73&abstractID=30897 2010.

60. Miyake H, Nelson C, Rennie PS et al. Testo­sterone-repressed prostate message-2 is an antiapoptotic gene involved in progression to androgen independence in prostate cancer. Cancer Res 2000; 60(1): 170–176.

61. July LV, Akbari M, Zellweger T et al. Clusterin expres­sion is significantly enhanced in prostate cancer cells following androgen withdrawal therapy. Prostate 2002; 50(3): 179–188.

62. Saad F, Hotte SJ, North SA et al. A phase II randomized study of custirsen (OGX-011) combination therapy in patients with poor-risk hormone refractory prostate cancer (HRPC) who relapsed on or within six months of 1st-line docetaxel therapy. J Clin Oncol 2008; 26.

63. Chi KN, Hotte JS, Yu EY et al. Randomized Phase II Study of Docetaxel and Prednisone With or Without OGX-011 in Patients With Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol 2010; 28(27): 4247–4254.

64. Krueckl SL, Sikes RA, Edlund NM et al. Increased insulin-like growth factor I receptor expression and signaling are components of androgen-independent progression in a lineage-derived prostate cancer progression model. Cancer Res 2004; 64(23): 8620–8629.

65. Higano C, Alumkal J, Ryan CJ et al. A phase II study evaluating the efficacy and safety of single agent IMC A12, a monoclonal antibody (MAb), against the insulin-like growth factor-1 receptor (IGF-IR), as monotherapy in patients with metastastic, asymptomatic castration-resistant prostate cancer (CRPC). J Clin Oncol 2009; 27.

66. Akhavan A, McHugh KH, Guruli G et al. Endothelin receptor A blockade enhances taxane effects in prostate cancer. Neoplasia 2006; 8(9): 725–732.

67. 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(9): 944–949.

68. 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 U S A 2003; 100(19): 10954–10959.

69. Carducci MA, Nelson JB, Bowling MK et al. Atra­sentan, an endothelin-receptor antagonist for refractory adenocarcinomas: safety and pharmacokinetics. J Clin Oncol 2002; 20(8): 2171–2180.

70. Carducci MA, Saad F, Abrahamsson PA et al. A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Cancer 2007; 110(9): 1959–1966.

71. Nelson JB, Love W, Chin JL et al. Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Cancer 2008; 113(9): 2478–2487.

72. James ND, Caty A, Payne H et al. Final safety and efficacy analysis of the specific endothelin A receptor antagonist zibotentan (ZD4054) in patients with meta­static castration-resistant prostate cancer and bone metastases who were pain-free or mildly symptomatic for pain: a double-blind, placebo-controlled, randomized Phase II trial. BJU Int 2010; 106(7): 966–973.

73. Peehl DM, Skowronski RJ, Leung GK et al. Anti­proli­ferative effects of 1,25-dihydroxyvitamin D3 on primary cultures of human prostatic cells. Cancer Res 1994; 54(3): 805–810.

74. Beer TM, Ryan CW, Venner PM et al. Double-blin­ded randomized study of high-dose calcitriol plusdocetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators. J Clin Oncol 2007; 25(6): 669–674.

75. Scher HI, Chi KN, De Wit R et al. Docetaxel (D) plus high-dose calcitriol versus D plus prednisone (P) for patients (Pts) with progressive castration-resistant prostate cancer (CRPC): Results from the phase III ASCENT2 trial. J Clin Oncol 2010; 28.

76. Weinfurt KP, Li Y, Castel LD et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005; 16(4): 579–584.

77. Diamond TH, Higano CS, Smith MR et al. Osteo­porosis in men with prostate carcinoma receiving androgen-deprivation therapy: recommendations for diagnosis and therapies. Cancer 2004; 100(5): 892–899.

78. Preston DM, Torrens JI, Harding P et al. Androgen deprivation in men with prostate cancer is associated with an increased rate of bone loss. Prostate Cancer Prostatic Dis 2002; 5(4): 304–310.

79. Smith MR, McGovern FJ, Zietman AL et al. Pami­dro­nate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 2001; 345(13): 948–955.

80. Smith MR, Eastham J, Gleason DM et al. Rando­mized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation the­rapy for nonmetastatic prostate cancer. J Urol 2003; 169(6): 2008–20012.

81. Saad F, Gleason DM, Murray R 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(11): 879–882.

82. 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(6): 644–650.

83. Eymard JC, Oudard S, Gravis G et al. Docetaxel reintroduction in patients with metastatic castration-resistant docetaxel-sensitive prostate cancer: a retrospective multicentre study. BJU Int 2010; 106(7): 974–978.

84. Di Lorenzo G, Buonerba C, Autorino R et al. Cas­tra­tion-resistant prostate cancer: current and emer­ging treatment strategies. Drugs 2010; 70(8): 983–1000.

85. Sartor AO, Oudard S, Ozguroglu M et al. Cabazi­taxel or mitoxantrone with prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel: Final results of a multinational phase III trial (TROPIC). Available at: http://www.asco.org/ascov2/Meetings/ /Abstracts?&vmview=abst_detail_view&confID=73&abstractID=30560 2010;Abstract 9.

86. Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 2008; 473(2): 139–146.

87. Fizazi K, Carducci MA, Smith MR et al. Deno­sumab versus zoledronic acid for treatment of bone metastasis in men with castration-resistant prostate cancer: a randomized, double-blind study. The Lancet 2011; 377(9768): 813–822.

88. Fizazi K. The role of Src in prostate cancer. Ann Oncol 2007; 18(11): 1765–1773.

89. Nam S, Kim D, Cheng JQ et al. Action of the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate cancer cells. Cancer Res 2005; 65(20): 9185–9189.

90. Araujo J, Armstrong AJ, Braud EL et al. Dasatinib and docetaxel combination treatment for patients with castration-resistant progressive prostate cancer: A phase I/II study (CA180086). J Clin Oncol 2009; 27.

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Paediatric urologist Urology
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