What's New in Hormone-refractory Prostate Cancer Treatment

Jun Hyuk Hong

doi:10.5124/jkma.2010.53.2.126

J Korean Med Assoc > Volume 53(2); 2010 > Article

Hong: What's New in Hormone-refractory Prostate Cancer Treatment

Focused Issue of This Month

Prostate Cancer

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2010; 53(2): 126-134.

Published online: February 28, 2010

DOI: http://dx.doi.org/10.5124/jkma.2010.53.2.126

What's New in Hormone-refractory Prostate Cancer Treatment

Jun Hyuk Hong, MD

Department of Urology, University of Ulsan College of Medicine, Korea. jhhong@amc.seoul.kr

Abstract

Prostate cancer represents the most common cancer in men in US and the fifth in men in Korea. For the patients with advanced prostate cancer, androgen deprivation therapy (ADT) remains the gold standard. However, patients with metastatic prostate cancer treated with ADT frequently develop hormone-refractory status (HRPC). Recent large randomized clinical trials demonstrated that docetaxel-based chemotherapy enhance survival and improve the quality of life in patients with HRPC. Although docetaxel-based chemotherapy has become the standard treatment for HRPC, PSA responses rarely exceed 50% and median survival is still less than 2 years. Therefore, there is a need for newer agents that can improve outcomes. This review focuses on the current therapies for the treatment of HRPC, including new cytotoxic agents, antiproliferative agents, antitumor vaccine and antiangiogenic agents. These approaches yielded expected or disappointing results in the phase II or III trials. Interpretation of these trials is sometimes complicated by discordant radiographic and PSA responses. Further investigation in search of more predictive new markers is warranted. Docetaxel-based chemotherapy has become the first-line standard treatment for HRPC, but the survival results are not satisfactory. Therefore, newer agents are being developed with promising results in phase II trials. These new agents should demonstrate higher patient survival rate in phase III studies on a larger scale in order to be approved for clinical use.

Prostatic neoplasms; Antineoplastic agents; Drug therapy; Prostate-specific antigen

References

1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-249.

2. Jung KW, Won YJ, Park S, Kong HJ, Sung J, Shin HR, Park EC, Lee JS. Cancer statistics in Korea: incidence, mortality and survival in 2005. J Korean Med Sci 2009;24:995-1003.

3. 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. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351:1502-1512.

4. Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 2008;26:242-245.

5. 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. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:1513-1520.

6. Collette L, Burzykowski T, Schroder FH. Prostate-specific antigen (PSA) alone is not an appropriate surrogate marker of long-term therapeutic benefit in prostate cancer trials. Eur J Cancer 2006;42:1344-1350.

7. Sternberg CN, Whelan P, Hetherington J, Paluchowska B, Slee PH, Vekemans K, Van Erps P, Theodore C, Koriakine O, Oliver T, Lebwohl D, Debois M, Zurlo A, Collette L. 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.

8. Sternberg CN, Petrylak DP, Sartor O, Witjes JA, Demkow T, Ferrero JM, Eymard JC, Falcon S, Calabro F, James N, Bodrogi I, Harper P, Wirth M, Berry W, Petrone ME, McKearn TJ, Noursalehi M, George M, Rozencweig M. 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;27:5431-5438.

9. Hussain M, Tangen CM, Lara PN Jr, Vaishampayan UN, Petrylak DP, Colevas AD, Sakr WA, Crawford ED. 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.

10. Rosenberg JE, Weinberg VK, Kelly WK, Michaelson D, Hussain MH, Wilding G, Gross M, Hutcheon D, Small EJ. Activity of second-line chemotherapy in docetaxel-refractory hormone-refractory prostate cancer patients : randomized phase 2 study of ixabepilone or mitoxantrone and prednisone. Cancer 2007;110:556-563.

11. Rosenberg JE, Ryan CJ, Weinberg VK, Smith DC, Hussain M, Beer TM, Ryan CW, Mathew P, Pagliaro LC, Harzstark AL, Sharib J, Small EJ. Phase I study of ixabepilone, mitoxantrone, and prednisone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel-based therapy: a study of the department of defense prostate cancer clinical trials consortium. J Clin Oncol 2009;27:2772-2778.

12. Chi KN, Beardsley EK, Venner PM. A phase II study of patupilone in patients with metastatic hormone refractory prostate cancer (HRPC) who have progressed after docetaxel. J Clin Oncol 2008;26:15S.

13. Hussain A, DiPaola RS, Baron AD, Higano CS, Tchekmedyian NS, Johri AR. Phase II trial of weekly patupilone in patients with castration-resistant prostate cancer. Ann Oncol 2009;20:492-497.

14. Morant R, Bernhard J, Dietrich D, Gillessen S, Bonomo M, Borner M, Bauer J, Cerny T, Rochlitz C, Wernli M, Gschwend A, Hanselmann S, Hering F, Schmid HP. Capecitabine in hormone-resistant metastatic prostatic carcinoma-a phase II trial. Br J Cancer 2004;90:1312-1317.

15. Vaishampayan UN, Marur S, Heilbrun LK, Cher ML, Dickow B, Smith DW, Al Hasan SA, Eliason J. Phase II trial of capecitabine and weekly docetaxel for metastatic castrate resistant prostate cancer. J Urol 2009;182:317-323.

16. Kolodziej M, Neubauer MA, Rousey SR, Pluenneke RE, Perrine G, Mull S, Boehm KA, Ilegbodu D, Asmar L. Phase II trial of docetaxel/capecitabine in hormone-refractory prostate cancer. Clin Genitourin Cancer 2006;5:155-161.

17. Ferrero JM, Chamorey E, Oudard S, Dides S, Lesbats G, Cavaglione G, Nouyrigat P, Foa C, Kaphan R. Phase II trial evaluating a docetaxel-capecitabine combination as treatment for hormone-refractory prostate cancer. Cancer 2006;107:738-745.

18. Attard G, Reid AH, A'Hern R, Parker C, Oommen NB, Folkerd E, Messiou C, Molife LR, Maier G, Thompson E, Olmos D, Sinha R, Lee G, Dowsett M, Kaye SB, Dearnaley D, Kheoh T, Molina A, de Bono JS. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol 2009;27:3742-3748.

19. Danila DC, Rathkopf DE, Morris MJ. Abiraterone acetate and prednisone in patients (Pts) with progressive metastatic castration resistant prostate cancer (CRPC) after failure of docetaxel-based chemotherapy, [Abstract #5019]. J Clin Oncol 2008;26:254S.

20. Beer TM, Eilers KM, Garzotto M, Egorin MJ, Lowe BA, Henner WD. Weekly high-dose calcitriol and docetaxel in metastatic androgen-independent prostate cancer. J Clin Oncol 2003;21:123-128.

21. Beer TM, Ryan CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD, Redfern CH, Fehrenbacher L, Saleh MN, Waterhouse DM, Carducci MA, Vicario D, Dreicer R, Higano CS, Ahmann FR, Chi KN, Henner WD, Arroyo A, Clow FW. Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators. J Clin Oncol 2007;25:669-674.

22. Ning YM, Arlen PM, Gulley JL. Phase II trial of thalidomide (T), bevacizumab (Bv), and docetaxel (Doc) in patients (pts) with metastatic castration-refractory prostate cancer (mCRPC) [abstract]. J Clin Oncol 2008;26:250S.

23. Picus J, Halabi S, Rini B. The use of bevacizumab with docetaxel and estramustine in hormone-refractory prostate cancer: initial results of CALGB 90006 [abstract]. Proc Am Soc Clin Oncol 2003;22:392a.

24. Di Lorenzo G, Figg WD, Fossa SD, Mirone V, Autorino R, Longo N, Imbimbo C, Perdona S, Giordano A, Giuliano M, Labianca R, De Placido S. Combination of bevacizumab and docetaxel in docetaxel-pretreated hormone-refractory prostate cancer: a phase 2 study. Eur Urol 2008;54:1089-1094.

25. Figg WD, Hussain MH, Gulley JL, Arlen PM, Aragon-Ching JB, Petrylak DP, Higano CS, Steinberg SM, Chatta GS, Parnes H, Wright JJ, Sartor O, Dahut WL. A double-blind randomized crossover study of oral thalidomide versus placebo for androgen dependent prostate cancer treated with intermittent androgen ablation. J Urol 2009;181:1104-1113. discussion 1113.

26. Figg WD, Dahut W, Duray P, Hamilton M, Tompkins A, Steinberg SM, Jones E, Premkumar A, Linehan WM, Floeter MK, Chen CC, Dixon S, Kohler DR, Kruger EA, Gubish E, Pluda JM, Reed E. A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer. Clin Cancer Res 2001;7:1888-1893.

27. Drake MJ, Robson W, Mehta P, Schofield I, Neal DE, Leung HY. An open-label phase II study of low-dose thalidomide in androgen-independent prostate cancer. Br J Cancer 2003;88:822-827.

28. Dahut WL, Gulley JL, Arlen PM, Liu Y, Fedenko KM, Steinberg SM, Wright JJ, Parnes H, Chen CC, Jones E, Parker CE, Linehan WM, Figg WD. Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer. J Clin Oncol 2004;22:2532-2539.

29. Romero S, Stanton G, DeFelice J, Schreiber F, Rago R, Fishman M. Phase II trial of thalidomide and daily oral dexamethasone for treatment of hormone refractory prostate cancer progressing after chemotherapy. Urol Oncol 2007;25:284-290.

30. Gallagher DJ, Milowsky MI, Gerst SR. Final results of a phase II study of sunitinib in patients with relapsed or refractory urothelial carcinoma. J Clin Oncol 2008;26:270S.

31. Sonpavde G, Periman PO, Bernold D, Weckstein D, Fleming MT, Galsky MD, Berry WR, Zhan F, Boehm KA, Asmar L, Hutson TE. Sunitinib malate for metastatic castration-resistant prostate cancer following docetaxel-based chemotherapy. Ann Oncol 2009.

32. Dror Michaelson M, Regan MM, Oh WK, Kaufman DS, Olivier K, Michaelson SZ, Spicer B, Gurski C, Kantoff PW, Smith MR. Phase II study of sunitinib in men with advanced prostate cancer. Ann Oncol 2009;20:913-920.

33. Steinbild S, Mross K, Frost A, Morant R, Gillessen S, Dittrich C, Strumberg D, Hochhaus A, Hanauske AR, Edler L, Burkholder I, Scheulen M. A clinical phase II study with sorafenib in patients with progressive hormone-refractory prostate cancer: a study of the CESAR Central European Society for Anticancer Drug Research-EWIV. Br J Cancer 2007;97:1480-1485.

34. Chi KN, Ellard SL, Hotte SJ, Czaykowski P, Moore M, Ruether JD, Schell AJ, Taylor S, Hansen C, Gauthier I, Walsh W, Seymour L. A phase II study of sorafenib in patients with chemonaive castration-resistant prostate cancer. Ann Oncol 2008;19:746-751.

35. Safarinejad MR. Safety and efficacy of sorafenib in patients with castrate resistant prostate cancer: A Phase II study. Urol Oncol 2008.

36. Aragon-Ching JB, Jain L, Gulley JL, Arlen PM, Wright JJ, Steinberg SM, Draper D, Venitz J, Jones E, Chen CC, Figg WD, Dahut WL. Final analysis of a phase II trial using sorafenib for metastatic castration-resistant prostate cancer. BJU Int 2009;103:1636-1640.

37. Yu EY, Wilding G, Posadas E, Gross M, Culine S, Massard C, Morris MJ, Hudes G, Calabro F, Cheng S, Trudel GC, Paliwal P, Sternberg CN. Phase II study of dasatinib in patients with metastatic castration-resistant prostate cancer. Clin Cancer Res 2009;15:7421-7428.

38. Carducci MA, Padley RJ, Breul J, Vogelzang NJ, Zonnenberg BA, Daliani DD, Schulman CC, Nabulsi AA, Humerickhouse RA, Weinberg MA, Schmitt JL, Nelson JB. 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.

39. Carducci MA, Saad F, Abrahamsson PA, Dearnaley DP, Schulman CC, North SA, Sleep DJ, Isaacson JD, Nelson JB. A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Cancer 2007;110:1959-1966.

40. Nelson JB, Love W, Chin JL. Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer [abstract]. J Clin Oncol 2007;25:237S.

41. Schelman WR, Liu G, Wilding G, Morris T, Phung D, Dreicer R. A phase I study of zibotentan (ZD4054) in patients with metastatic, castrate-resistant prostate cancer. Invest New Drugs 2009.

42. James ND, Caty A, Borre M, Zonnenberg BA, Beuzeboc P, Morris T, Phung D, Dawson NA. Safety and efficacy of the specific endothelin-A receptor antagonist ZD4054 in patients with hormone-resistant prostate cancer and bone metastases who were pain free or mildly symptomatic: a double-blind, placebo-controlled, randomised, phase 2 trial. Eur Urol 2009;55:1112-1123.

43. Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW. 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;115:3670-3679.

44. Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM. 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;24:3089-3094.

45. Fagerberg J. Granulocyte-macrophage colony-stimulating factor as an adjuvant in tumor immunotherapy. Med Oncol 1996;13:155-160.

46. Small EJ, Reese DM, Um B, Whisenant S, Dixon SC, Figg WD. Therapy of advanced prostate cancer with granulocyte macrophage colony-stimulating factor. Clin Cancer Res 1999;5:1738-1744.

47. Vogelzang NJ. One hundred thirteen men with hormone-refractory prostate cancer died today. J Clin Oncol 1996;14:1753-1755.

48. Corman J, Small E, Smith D. Immunotherapy with GVAX vaccine for prostate cancer improves predicted survival in metastatic hormone refractory prostate cancer: results from two phase 2 studies, [Abstract #976]. J Urol 2006;175.

49. Higano CS, Corman JM, Smith DC, Centeno AS, Steidle CP, Gittleman M, Simons JW, Sacks N, Aimi J, Small EJ. Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer. Cancer 2008;113:975-984.

50. Small EJ, Sacks N, Nemunaitis J, Urba WJ, Dula E, Centeno AS, Nelson WG, Ando D, Howard C, Borellini F, Nguyen M, Hege K, Simons JW. Granulocyte macrophage colony-stimulating factor-secreting allogeneic cellular immunotherapy for hormone-refractory prostate cancer. Clin Cancer Res 2007;13:3883-3891.

51. Cell Genesys Halts VITAL-2 GVAX Trial in Advanced Prostate Cancer. Drugs.com Accessed Dec 30, 2009. Available at: http://www.drugs.com/news/cell-genesys-halts-vital-2-gvax-trial-advanced-prostate-cancer-13371.html

52. Cell Genesys Announces Termination of VITAL-1 Phase 3 Trial of GVAX Immunotherapy for Prostate Cancer. Drugs.com Accessed Dec 30, 2009. Available at: http://www.drugs.com/news/cell-genesys-announces-termination-vital-1-phase-3-trial-gvax-immunotherapyprostate-cancer-14159.html

53. Madan RA, Arlen PM, Mohebtash M, Hodge JW, Gulley JL. Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer. Expert Opin Investig Drugs 2009;18:1001-1011.

54. Arlen PM, Skarupa L, Pazdur M, Seetharam M, Tsang KY, Grosenbach DW, Feldman J, Poole DJ, Litzinger M, Steinberg SM, Jones E, Chen C, Marte J, Parnes H, Wright J, Dahut W, Schlom J, Gulley JL. Clinical safety of a viral vector based prostate cancer vaccine strategy. J Urol 2007;178(4 Pt 1):1515-1520.

55. Arlen PM, Gulley JL, Parker C, Skarupa L, Pazdur M, Panicali D, Beetham P, Tsang KY, Grosenbach DW, Feldman J, Steinberg SM, Jones E, Chen C, Marte J, Schlom J, Dahut W. A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer. Clin Cancer Res 2006;12:1260-1269.

56. Lubaroff DM, Konety BR, Link B, Gerstbrein J, Madsen T, Shannon M, Howard J, Paisley J, Boeglin D, Ratliff TL, Williams RD. Phase I clinical trial of an adenovirus/prostate-specific antigen vaccine for prostate cancer: safety and immunologic results. Clin Cancer Res 2009;15:7375-7380.

57. Tolcher AW, Chi K, Kuhn J, Gleave M, Patnaik A, Takimoto C, Schwartz G, Thompson I, Berg K, D'Aloisio S, Murray N, Frankel SR, Izbicka E, Rowinsky E. 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.

58. Sternberg CN, Dumez H, Van Poppel H, Skoneczna I, Sella A, Daugaard G, Gil T, Graham J, Carpentier P, Calabro F, Collette L, Lacombe D. Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer. Ann Oncol 2009;20:1264-1269.

59. Liu G, Kelly WK, Wilding G, Leopold L, Brill K, Somer B. An open-label, multicenter, phase I/II study of single-agent AT-101 in men with castrate-resistant prostate cancer. Clin Cancer Res 2009;15:3172-3176.