Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Evolving standards in the treatment of docetaxel-refractory castration-resistant prostate cancer

Prostate Cancer and Prostatic Diseases volume 14, pages 192–205 (2011)Cite this article

Subjects

Abstract

The management of men with metastatic castration-resistant prostate cancer (CRPC) has taken several leaps forward in the past year, with the demonstration of improved overall survival with three novel agents (sipuleucel-T, cabazitaxel with prednisone and abiraterone acetate with prednisone), and a significant delay in skeletal-related events observed with denosumab. The pipeline of systemic therapies in prostate cancer remains strong, as multiple agents with a diverse array of mechanisms of action are showing preliminary signs of clinical benefit, leading to more definitive phase III confirmatory trials. In this review, which represents part 1 of a two-part series on metastatic CRPC, we will summarize the mechanisms of resistance to hormonal and chemotherapies and discuss the evolving landscape of treatment options for men with CRPC, with a particular focus on currently approved and emerging treatment options following docetaxel administration, as well as prognostic factors in this post-docetaxel state. As docetaxel remains the standard initial systemic therapy for men with metastatic CRPC for both palliative and life-prolonging purposes, knowledge of these evolving standards will help to optimize delivery of care and long-term outcomes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Xu J, Ward E . Cancer statistics, 2010. CA Cancer J Clin 2010; 60: 277–300.

    Article  PubMed  Google Scholar 

  2. 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  PubMed  Google Scholar 

  3. 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  PubMed  Google Scholar 

  4. 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. J Clin Oncol 1996; 14: 1756–1764.

    Article  CAS  PubMed  Google Scholar 

  5. de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I 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: 1147–1154.

    Article  CAS  PubMed  Google Scholar 

  6. de Bono JS, Logothetis CJ, Fizazi K, North S, Chu L, Chi KN et al. Abiraterone acetate plus low-dose prednisone improves overall survival in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel-based chemotherapy: results of COU-AA-301, a randomized double-blind placebo-controlled phase III study. Ann Oncol 2010; 21 (Suppl 8); abstract LBA5.

  7. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363: 411–422.

    Article  CAS  PubMed  Google Scholar 

  8. Feldman BJ, Feldman D . The development of androgen-independent prostate cancer. Nat Rev Cancer 2001; 1: 34–45.

    Article  CAS  PubMed  Google Scholar 

  9. Gelmann EP . Molecular biology of the androgen receptor. J Clin Oncol 2002; 20: 3001–3015.

    Article  CAS  PubMed  Google Scholar 

  10. Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R et al. Molecular determinants of resistance to antiandrogen therapy. Nat Med 2004; 10: 33–39.

    Article  CAS  PubMed  Google Scholar 

  11. Tomlins SA, Mehra R, Rhodes DR, Cao X, Wang L, Dhanasekaran SM et al. Integrative molecular concept modeling of prostate cancer progression. Nat Genet 2007; 39: 41–51.

    Article  CAS  PubMed  Google Scholar 

  12. Koivisto P, Kononen J, Palmberg C, Tammela T, Hyytinen E, Isola J et al. Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res 1997; 57: 314–319.

    CAS  PubMed  Google Scholar 

  13. Taplin ME, Bubley GJ, Shuster TD, Frantz ME, Spooner AE, Ogata GK et al. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med 1995; 332: 1393–1398.

    Article  CAS  PubMed  Google Scholar 

  14. Sun S, Sprenger CC, Vessella RL, Haugk K, Soriano K, Mostaghel EA et al. Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. J Clin Invest 2010; 120: 2715–2730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nupponen N, Visakorpi T . Molecular biology of progression of prostate cancer. Eur Urol 1999; 35: 351–354.

    Article  CAS  PubMed  Google Scholar 

  16. Tamura K, Furihata M, Tsunoda T, Ashida S, Takata R, Obara W et al. Molecular features of hormone-refractory prostate cancer cells by genome-wide gene expression profiles. Cancer Res 2007; 67: 5117–5125.

    Article  CAS  PubMed  Google Scholar 

  17. Gregory CW, Johnson Jr RT, Mohler JL, French FS, Wilson EM . Androgen receptor stabilization in recurrent prostate cancer is associated with hypersensitivity to low androgen. Cancer Res 2001; 61: 2892–2898.

    CAS  PubMed  Google Scholar 

  18. Brooke GN, Bevan CL . The role of androgen receptor mutations in prostate cancer progression. Curr Genomics 2009; 10: 18–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hu R, Dunn TA, Wei S, Isharwal S, Veltri RW, Humphreys E et al. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res 2009; 69: 16–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Watson PA, Chen YF, Balbas MD, Wongvipat J, Socci ND, Viale A et al. Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor. Proc Natl Acad Sci USA 2010; 107: 16759–16765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mostaghel EA, Page ST, Lin DW, Fazli L, Coleman IM, True LD et al. Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res 2007; 67: 5033–5041.

    Article  CAS  PubMed  Google Scholar 

  22. Stigliano A, Gandini O, Cerquetti L, Gazzaniga P, Misiti S, Monti S et al. Increased metastatic lymph node 64 and CYP17 expression are associated with high stage prostate cancer. J Endocrinol 2007; 194: 55–61.

    Article  CAS  PubMed  Google Scholar 

  23. Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res 2006; 66: 2815–2825.

    Article  CAS  PubMed  Google Scholar 

  24. Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res 2008; 68: 4447–4454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Reid AH, Attard G, Barrie E, de Bono JS . CYP17 inhibition as a hormonal strategy for prostate cancer. Nat Clin Pract Urol 2008; 5: 610–620.

    Article  CAS  PubMed  Google Scholar 

  26. Zhou HJ, Yan J, Luo W, Ayala G, Lin SH, Erdem H et al. SRC-3 is required for prostate cancer cell proliferation and survival. Cancer Res 2005; 65: 7976–7983.

    Article  CAS  PubMed  Google Scholar 

  27. Shi XB, Xue L, Zou JX, Gandour-Edwards R, Chen H, deVere White RW . Prolonged androgen receptor loading onto chromatin and the efficient recruitment of p160 coactivators contribute to androgen-independent growth of prostate cancer cells. Prostate 2008; 68: 1816–1826.

    Article  CAS  PubMed  Google Scholar 

  28. Xu J, Wu RC, O’Malley BW . Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family. Nat Rev Cancer 2009; 9: 615–630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS et al. Integrative genomic profiling of human prostate cancer. Cancer Cell 2010; 18: 11–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lakshmikanthan V, Zou L, Kim JI, Michal A, Nie Z, Messias NC et al. Identification of betaArrestin2 as a corepressor of androgen receptor signaling in prostate cancer. Proc Natl Acad Sci USA 2009; 106: 9379–9384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Attar RM, Takimoto CH, Gottardis MM . Castration-resistant prostate cancer: locking up the molecular escape routes. Clin Cancer Res 2009; 15: 3251–3255.

    Article  CAS  PubMed  Google Scholar 

  32. Zhu ML, Kyprianou N . Androgen receptor and growth factor signaling cross-talk in prostate cancer cells. Endocr Relat Cancer 2008; 15: 841–849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Craft N, Shostak Y, Carey M, Sawyers CL . A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat Med 1999; 5: 280–285.

    Article  CAS  PubMed  Google Scholar 

  34. Mellinghoff IK, Vivanco I, Kwon A, Tran C, Wongvipat J, Sawyers CL . HER2/neu kinase-dependent modulation of androgen receptor function through effects on DNA binding and stability. Cancer Cell 2004; 6: 517–527.

    Article  CAS  PubMed  Google Scholar 

  35. Wang G, Wang J, Sadar MD . Crosstalk between the androgen receptor and beta-catenin in castrate-resistant prostate cancer. Cancer Res 2008; 68: 9918–9927.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Desai SJ, Ma AH, Tepper CG, Chen HW, Kung HJ . Inappropriate activation of the androgen receptor by non-steroids: involvement of the Src kinase pathway and its therapeutic implications. Cancer Res 2006; 66: 10449–10459.

    Article  CAS  PubMed  Google Scholar 

  37. Raffo AJ, Perlman H, Chen MW, Day ML, Streitman JS, Buttyan R . Overexpression of Bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. Cancer Res 1995; 55: 4438–4445.

    CAS  PubMed  Google Scholar 

  38. Yang CC, Lin HP, Chen CS, Yang YT, Tseng PH, Rangnekar VM et al. Bcl-xL mediates a survival mechanism independent of the phosphoinositide 3-kinase/Akt pathway in prostate cancer cells. J Biol Chem 2003; 278: 25872–25878.

    Article  CAS  PubMed  Google Scholar 

  39. Zhang M, Latham DE, Delaney MA, Chakravarti A . Survivin mediates resistance to antiandrogen therapy in prostate cancer. Oncogene 2005; 24: 2474–2482.

    Article  CAS  PubMed  Google Scholar 

  40. Trédan O, Galmarini CM, Patel K, Tannock IF . Drug resistance and the solid tumor micro-environment. J Natl Cancer Inst 2007; 99: 1441–1454.

    Article  CAS  PubMed  Google Scholar 

  41. Brown JM, Wilson WR . Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 2004; 4: 437–447.

    Article  CAS  PubMed  Google Scholar 

  42. Kyle AH, Huxham LA, Yeoman DM, Minchinton AI . Limited tissue penetration of taxanes: a mechanism for resistance in solid tumors. Clin Cancer Res 2007; 13: 2804–2810.

    Article  CAS  PubMed  Google Scholar 

  43. Heldin CH, Rubin K, Pietras K, Ostman A . High interstitial fluid pressure: an obstacle in cancer therapy. Nat Rev Cancer 2004; 4: 806–813.

    Article  CAS  PubMed  Google Scholar 

  44. Semenza GL . Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 2010; 29: 625–634.

    Article  CAS  PubMed  Google Scholar 

  45. Maxwell PJ, Gallagher R, Seaton A, Wilson C, Scullin P, Pettigrew J et al. HIF-1 and NFκB-mediated upregulation of CXCR1 and CXCR2 expression promotes cell survival in hypoxic prostate cancer cells. Oncogene 2007; 26: 7333–7345.

    Article  CAS  PubMed  Google Scholar 

  46. Meads MB, Gatenby RA, Dalton WS . Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat Rev Cancer 2009; 9: 665–674.

    Article  CAS  PubMed  Google Scholar 

  47. Kobayashi H, Man S, Graham CH, Kapitain SJ, Teicher BA, Kerbel RS . Acquired multicellular-mediated resistance to alkylating agents in cancer. Proc Natl Acad Sci USA 1993; 90: 3294–3298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Giannoni E, Bianchini F, Masieri L, Serni S, Torre E, Calorini L et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial–mesenchymal transition and cancer stemness. Cancer Res 2010; 70: 6945–6956.

    Article  CAS  PubMed  Google Scholar 

  49. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY et al. The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133: 704–715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 2009; 138: 645–659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gravdal K, Halvorsen OJ, Haukaas SA, Akslen LA . A switch from E-cadherin to N-cadherin expression indicates epithelial-to-mesenchymal transition and is of strong and independent importance for the progress of prostate cancer. Clin Cancer Res 2007; 13: 7003–7011.

    Article  CAS  PubMed  Google Scholar 

  52. Tanaka H, Kono E, Tran CP, Miyazaki H, Yamashiro J, Shimomura T et al. Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance. Nat Med 2010; 16: 1414–1420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Logothetis CJ, Navone NM, Lin SH . Understanding the biology of bone metastases: key to the effective treatment of prostate cancer. Clin Cancer Res 2008; 14: 1599–1602.

    Article  CAS  PubMed  Google Scholar 

  54. Zhang J, Lu Y, Pienta KJ . Multiple roles of chemokine (C–C motif) ligand 2 in promoting prostate cancer growth. J Natl Cancer Inst 2010; 102: 522–528.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Qian DZ, Rademacher BL, Pittsenbarger J, Huang CY, Myrthue A, Higano CS et al. CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel-induced cytotoxicity. Prostate 2010; 70: 433–442.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Kavallaris M . Microtubules and resistance to tubulin-binding agents. Nat Rev Cancer 2010; 10: 194–204.

    Article  CAS  PubMed  Google Scholar 

  57. Bradshaw DM, Arceci RJ . Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance. J Clin Oncol 1998; 16: 3674–3690.

    Article  CAS  PubMed  Google Scholar 

  58. Rowinsky EK, Smith L, Wang YM, Chaturvedi P, Villalona M, Campbell E et al. Phase I and pharmacokinetic study of paclitaxel in combination with biricodar, a novel agent that reverses multidrug resistance conferred by overexpression of both MDR1 and MRP1. J Clin Oncol 1998; 16: 2964–2976.

    Article  CAS  PubMed  Google Scholar 

  59. Borst P, Evers R, Kool M, Wijnholds J . A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst 2000; 92: 1295–1302.

    Article  CAS  PubMed  Google Scholar 

  60. Gottesman MM, Fojo T, Bates SE . Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2002; 2: 48–58.

    Article  CAS  PubMed  Google Scholar 

  61. Berrieman HK, Lind MJ, Cawkwell L . Do β-tubulin mutations have a role in resistance to chemotherapy? Lancet Oncol 2004; 5: 158–164.

    Article  CAS  PubMed  Google Scholar 

  62. Sève P, Dumontet C . Is class III β-tubulin a predictive factor in patients receiving tubulin-binding agents? Lancet Oncol 2008; 9: 168–175.

    Article  CAS  PubMed  Google Scholar 

  63. van Amerongen R, Berns A . TXR1-mediated thrombospondin repression: a novel mechanism of resistance to taxanes? Genes Dev 2006; 20: 1975–1981.

    Article  CAS  PubMed  Google Scholar 

  64. Whipple RA, Matrone MA, Cho EH, Balzer EM, Vitolo MI, Yoon JR et al. Epithelial-to-mesenchymal transition promotes tubulin detyrosination and microtentacles that enhance endothelial engagement. Cancer Res 2010; 70: 8127–8137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Verrills NM, Po’uha ST, Liu ML, Liaw TY, Larsen MR, Ivery MT et al. Alterations in γ-actin and tubulin-targeted drug resistance in childhood leukemia. J Natl Cancer Inst 2006; 98: 1363–1374.

    Article  CAS  PubMed  Google Scholar 

  66. Haldar S, Basu A, Croce CM . Bcl2 is the guardian of microtubule integrity. Cancer Res 1997; 57: 229–233.

    CAS  PubMed  Google Scholar 

  67. Yamanaka K, Rocchi P, Miyake H, Fazli L, So A, Zangemeister-Wittke U et al. Induction of apoptosis and enhancement of chemosensitivity in human prostate cancer LNCaP cells using bispecific antisense oligonucleotide targeting Bcl-2 and Bcl-xL genes. BJU Int 2006; 97: 1300–1308.

    Article  CAS  PubMed  Google Scholar 

  68. Zoubeidi A, Chi K, Gleave M . Targeting the cytoprotective chaperone, clusterin, for treatment of advanced cancer. Clin Cancer Res 2010; 16: 1088–1093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Pchejetski D, Doumerc N, Golzio M, Naymark M, Teissié J, Kohama T et al. Chemosensitizing effects of sphingosine kinase-1 inhibition in prostate cancer cell and animal models. Mol Cancer Ther 2008; 7: 1836–1845.

    Article  CAS  PubMed  Google Scholar 

  70. Mumenthaler SM, Ng PY, Hodge A, Bearss D, Berk G, Kanekal S et al. Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes. Mol Cancer Ther 2009; 8: 2882–2893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wu L, Birle DC, Tannock IF . Effects of the mammalian target of rapamycin inhibitor CCI-779 used alone or with chemotherapy on human prostate cancer cells and xenografts. Cancer Res 2005; 65: 2825–2831.

    Article  CAS  PubMed  Google Scholar 

  72. Boldt S, Weidle UH, Kolch W . The role of MAPK pathways in the action of chemotherapeutic drugs. Carcinogenesis 2002; 23: 1831–1838.

    Article  CAS  PubMed  Google Scholar 

  73. Zelivianski S, Spellman M, Kellerman M, Kakitelashvilli V, Zhou XW, Lugo E et al. ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells. Int J Cancer 2003; 107: 478–485.

    Article  CAS  PubMed  Google Scholar 

  74. Domingo-Domenech J, Oliva C, Rovira A, Codony-Servat J, Bosch M, Filella X et al. Interleukin 6, a nuclear factor-kappaB target, predicts resistance to docetaxel in hormone-independent prostate cancer and nuclear factor-kappaB inhibition by PS-1145 enhances docetaxel antitumor activity. Clin Cancer Res 2006; 12: 5578–5586.

    Article  CAS  PubMed  Google Scholar 

  75. Mimeault M, Johansson SL, Vankatraman G, Moore E, Henichart JP, Depreux P et al. Combined targeting of epidermal growth factor receptor and hedgehog signaling by gefitinib and cyclopamine cooperatively improves the cytotoxic effects of docetaxel on metastatic prostate cancer cells. Mol Cancer Ther 2007; 6: 967–978.

    Article  CAS  PubMed  Google Scholar 

  76. Banerjee S, Hussain M, Wang Z, Saliganan A, Che M, Bonfil D et al. In vitro and in vivo molecular evidence for better therapeutic efficacy of ABT-627 and taxotere combination in prostate cancer. Cancer Res 2007; 67: 3818–3826.

    Article  CAS  PubMed  Google Scholar 

  77. LoNigro C, Maffi M, Fischel JL, Formento P, Milano G, Merlano M . The combination of docetaxel and the somatostatin analogue lanreotide on androgen-independent docetaxel-resistant prostate cancer: experimental data. BJU Int 2008; 102: 622–627.

    Article  CAS  Google Scholar 

  78. Pivot X, Koralewski P, Hidalgo JL, Chan A, Gonçalves A, Schwartsmann G et al. A multicenter phase II study of XRP6258 administered as a 1-h intravenous infusion every 3 weeks in taxane-resistant metastatic breast cancer patients. Ann Oncol 2008; 19: 1547–1552.

    Article  CAS  PubMed  Google Scholar 

  79. Galsky MD, Dritselis A, Kirkpatrick P, Oh WK . Cabazitaxel. Nat Rev Drug Discov 2010; 9: 677–678.

    Article  CAS  PubMed  Google Scholar 

  80. Attard G, Greystoke A, Kaye S, de Bono J . Update on tubulin-binding agents. Pathol Biol 2006; 54: 72–84.

    Article  CAS  PubMed  Google Scholar 

  81. Mita AC, Denis LJ, Rowinsky EK, de Bono JS, Goetz AD, Ochoa L et al. Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1-h infusion every 3 weeks in patients with advanced solid tumors. Clin Cancer Res 2009; 15: 723–730.

    Article  CAS  PubMed  Google Scholar 

  82. FDA CfDEaR. Approval Package for Jevtana (NDA 20-1023). http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000Approv.pdf. (Published: 17 June 2010; accessed: 4 March 2011).

  83. Mohler J, Bahnson RR, Boston B, Busby JE, D’Amico A, Eastham JA et al. NCCN clinical practice guidelines in oncology: prostate cancer. J Natl Compr Cancer Netw 2010; 8: 162–200.

    Article  CAS  Google Scholar 

  84. Berthold DR, Pond GR, de Wit R, Eisenberger M, Tannock IF . Survival and PSA response of patients in the TAX 327 study who crossed over to receive docetaxel after mitoxantrone or vice versa. Ann Oncol 2008; 19: 1749–1753.

    Article  CAS  PubMed  Google Scholar 

  85. Rosenberg JE, Weinberg VK, Kelly WK, Michaelson D, Hussain MH, Wilding G et al. 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.

    Article  CAS  PubMed  Google Scholar 

  86. Eymard JC, Oudard S, Gravis G, Ferrero JM, Theodore C, Joly F et al. Docetaxel reintroduction in patients with metastatic castration-resistant docetaxel-sensitive prostate cancer: a retrospective multicentre study. BJU Int 2010; 106: 974–978.

    Article  CAS  PubMed  Google Scholar 

  87. Beer TM, Ryan CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD et al. Intermittent chemotherapy in patients with metastatic androgen-independent prostate cancer: results from ASCENT, a double-blinded, randomized comparison of high-dose calcitriol plus docetaxel with placebo plus docetaxel. Cancer 2008; 112: 326–330.

    Article  CAS  PubMed  Google Scholar 

  88. Di Lorenzo G, Buonerba C, Faiella A, Rescigno P, Rizzo M, Autorino R et al. Phase II study of docetaxel re-treatment in docetaxel-pretreated castration-resistant prostate cancer. BJU Int 2010; 107: 234–239.

    Article  CAS  Google Scholar 

  89. Loriot Y, Massard C, Gross-Goupil M, Di Palma M, Escudier B, Bossi A 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: 1770–1772.

    Article  CAS  PubMed  Google Scholar 

  90. Ross RW, Beer TM, Jacobus S, Bubley GJ, Taplin ME, Ryan CW et al. A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel. Cancer 2008; 112: 521–526.

    Article  CAS  PubMed  Google Scholar 

  91. Trimble EL, Adams JD, Vena D, Hawkins MJ, Friedman MA, Fisherman JS et al. Paclitaxel for platinum-refractory ovarian cancer: results from the first 1000 patients registered to National Cancer Institute Treatment Referral Center 9103. J Clin Oncol 1993; 11: 2405–2410.

    Article  CAS  PubMed  Google Scholar 

  92. Berry W, Friedland D, Fleagle J, Jackson D, Ilegbodu D, Boehm KA et al. A phase II study of weekly paclitaxel/estramustine/carboplatin in hormone-refractory prostate cancer. Clin Genitourin Cancer 2006; 5: 131–137.

    Article  CAS  PubMed  Google Scholar 

  93. Cabrespine A, Guy L, Khenifar E, Curé H, Fleury J, Penault-Llorca F et al. Randomized Phase II study comparing paclitaxel and carboplatin versus mitoxantrone in patients with hormone-refractory prostate cancer. Urology 2006; 67: 354–359.

    Article  PubMed  Google Scholar 

  94. Jeske S, Tagawa ST, Olowokure O, Selzer J, Giannakakou P, Nanus DM . Carboplatin plus paclitaxel therapy after docetaxel in men with metastatic castrate resistant prostate cancer. Urol Oncol 2010 (E-pub ahead of print).

  95. Roche M, Kyriakou H, Seiden M . Drug evaluation: tesetaxel, an oral semi-synthetic taxane derivative. Curr Opin Invest Drugs 2006; 7: 1092–1099.

    CAS  Google Scholar 

  96. Shionoya M, Jimbo T, Kitagawa M, Soga T, Tohgo A . DJ-927, a novel oral taxane, overcomes P-glycoprotein-mediated multidrug resistance in vitro and in vivo. Cancer Sci 2003; 94: 459–466.

    Article  CAS  PubMed  Google Scholar 

  97. Baas P, Szczesna A, Albert I, Milanowski J, Juhász E, Sztancsik Z et al. Phase I/II study of a 3-weekly oral taxane (DJ-927) in patients with recurrent, advanced non-small cell lung cancer. J Thorac Oncol 2008; 3: 745–750.

    Article  PubMed  Google Scholar 

  98. Modiano MR, Plezia P, Basche M, Cohn AL, Baram Y, Tapolsky G et al. A phase I study of TPI-287, a novel taxane, administered every 21 days in patients with advanced cancer. J Clin Oncol 2008; 26 (Suppl); abstract 13510.

  99. Gross M, Pendergrass K, Leitner S, Leichman G, Pugliese L, Silberman S . TPI-287, a third-generation taxane, is active and well tolerated as 2nd line therapy after failure of docetaxel in hormone-refractory prostate cancer. J Clin Oncol 2008; 26 (Suppl); abstract 16130.

  100. Gerth K, Bedorf N, Hofle G, Irschik H, Reichenbach H . Epothilones A and B: antifungal and cytotoxic compounds from Sorangium cellulosum (myxobacteria). Production, physicochemical and biological properties. J Antibiot 1996; 49: 560–563.

    Article  CAS  Google Scholar 

  101. Lee JJ, Kelly WK . Epothilones: tubulin polymerization as a novel target for prostate cancer therapy. Nat Clin Pract Oncol 2009; 6: 85–92.

    Article  CAS  PubMed  Google Scholar 

  102. Rivera E, Lee J, Davies A . Clinical development of ixabepilone and other epothilones in patients with advanced solid tumors. Oncologist 2008; 13: 1207–1223.

    Article  CAS  PubMed  Google Scholar 

  103. Hussain M, Tangen CM, Lara PN, Vaishampayan UN, Petrylak DP, Colevas AD 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.

    Article  PubMed  Google Scholar 

  104. Harzstark AL, Rosenberg JE, Weinberg VK, Sharib J, Ryan CJ, Smith DC et al. Ixabepilone, mitoxantrone, and prednisone for metastatic castration-resistant prostate cancer after docetaxel-based therapy: a phase 2 study of the department of defense prostate cancer clinical trials consortium. Cancer 2010; (E-pub ahead of print).

  105. Bystricky B, Chau I . Patupilone in cancer treatment. Expert Opin Invest Drugs 2011; 20: 107–117.

    Article  CAS  Google Scholar 

  106. Beardsley EK, Saad F, Eigl B, Venner P, Hotte S, Winquist E et al. A phase II study of patupilone in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel. J Clin Oncol 2009; 27 (Suppl); abstract 5139.

  107. Chatta GS, Feinstein TM, Appleman LJ, Friedland DM, Jacobs SA, Evans TL et al. Oxaliplatin and docetaxel in castration-resistant prostate cancer patients treated with up to two prior chemotherapeutic regimens: updated results of a phase II trial. J Clin Oncol 2008; 26 (Suppl); abstract 5148.

  108. Sella A, Yarom N, Zisman A, Kovel S . Paclitaxel, estramustine and carboplatin combination chemotherapy after initial docetaxel-based chemotherapy in castration-resistant prostate cancer. Oncology 2009; 76: 442–446.

    Article  CAS  PubMed  Google Scholar 

  109. Loriot Y, Massard C, Gross-Goupil M, Di Palma M, Escudier B, Bossi A et al. Combining carboplatin and etoposide in docetaxel-pretreated patients with castration-resistant prostate cancer: a prospective study evaluating also neuroendocrine features. Ann Oncol 2009; 20: 703–738.

    Article  CAS  PubMed  Google Scholar 

  110. Dorff TB, Groshen SG, Wei D, Korn C, Goldkorn A, Quinn DI et al. Interim results of a phase II trial of pemetrexed and oxaliplatin as 2nd/3rd-line therapy in hormone-refractory prostate cancer. J Clin Oncol 2008; 26 (Suppl); abstract 5139.

    Article  Google Scholar 

  111. Blesa JM, Marco VG, Giner-Bosch V, Cerezuela P, Candel VA . Phase II trial of oxaliplatin and capecitabine after progression of first-line chemotherapy in androgen-independent prostate cancer patients. Am J Clin Oncol 2010; 34: 155–159.

    Google Scholar 

  112. Papandreou CN, Daliani DD, Thall PF, Tu SM, Wang X, Reyes A et al. Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the prostate. J Clin Oncol 2002; 20: 3072–3080.

    Article  CAS  PubMed  Google Scholar 

  113. Spiess PE, Pettaway CA, Vakar-Lopez F, Kassouf W, Wang X, Busby JE et al. Treatment outcomes of small cell carcinoma of the prostate: a single-center study. Cancer 2007; 110: 1729–1737.

    Article  PubMed  Google Scholar 

  114. Brennan SM, Gregory DL, Stillie A, Herschtal A, MacManus M, Ball DL . Should extrapulmonary small cell cancer be managed like small cell lung cancer? Cancer 2010; 116: 888–895.

    Article  PubMed  Google Scholar 

  115. Oh WK, Tay MH, Huang J . Is there a role for platinum chemotherapy in the treatment of patients with hormone-refractory prostate cancer? Cancer 2007; 109: 477–486.

    Article  CAS  PubMed  Google Scholar 

  116. Sternberg CN . Satraplatin in the treatment of hormone-refractory prostate cancer. BJU Int 2005; 96: 990–994.

    Article  CAS  PubMed  Google Scholar 

  117. Sternberg CN, Petrylak DP, Sartor O, Witjes JA, Demkow T, Ferrero JM 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: 5431–5438.

    Article  CAS  PubMed  Google Scholar 

  118. O’Donnell A, Judson I, Dowsett M, Raynaud F, Dearnaley D, Mason M et al. Hormonal impact of the 17α-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer 2004; 90: 2317–2325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Attard G, Reid AH, Yap TA, Raynaud F, Dowsett M, Settatree S et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 2008; 26: 4563–4571.

    Article  CAS  PubMed  Google Scholar 

  120. Attard G, Reid AH, de Bono JS . Abiraterone acetate is well tolerated without concomitant use of corticosteroids. J Clin Oncol 2010; 28: e560–e561.

    Article  PubMed  Google Scholar 

  121. Attard G, Reid AH, A’Hern R, Parker C, Oommen NB, Folkerd E 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: 3742–3748.

    Article  CAS  PubMed  Google Scholar 

  122. Ryan CJ, Smith MR, Fong L, Rosenberg JE, Kantoff P, Raynaud F 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: 1481–1488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Reid AH, Attard G, Danila DC, Oommen NB, Olmos D, Fong PC et al. Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate. J Clin Oncol 2010; 28: 1489–1495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Danila DC, Morris MJ, de Bono JS, Ryan CJ, Denmeade SR, Smith MR 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: 1496–1501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Scher HI, Jia X, de Bono JS, Fleisher M, Pienta KJ, Raghavan D et al. Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol 2009; 10: 233–239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 2008; 14: 6302–6309.

    Article  CAS  PubMed  Google Scholar 

  127. Trachtenberg J, Zadra J . Steroid synthesis inhibition by ketoconazole: sites of action. Clin Invest Med 1988; 11: 1–5.

    CAS  PubMed  Google Scholar 

  128. Ryan CJ, Eisenberger M . Chemotherapy for hormone-refractory prostate cancer: now it's a question of when? J Clin Oncol 2005; 23: 8242–8246.

    Article  CAS  PubMed  Google Scholar 

  129. Small EJ, Halabi S, Dawson NA, Stadler WM, Rini BI, Picus J 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.

    Article  CAS  PubMed  Google Scholar 

  130. Galsky MD, Simon K, Sonpavde G, Hutson TE, Fleming M, Kondagunta GV et al. Ketoconazole retains activity in patients with docetaxel-refractory prostate cancer. Ann Oncol 2009; 20: 965–966.

    Article  CAS  PubMed  Google Scholar 

  131. Nakabayashi M, Oh WK, Jacobus S, Regan MM, Taplin ME, Kantoff PW et al. Activity of ketoconazole after taxane-based chemotherapy in castration-resistant prostate cancer. BJU Int 2010; 105: 1392–1396.

    Article  CAS  PubMed  Google Scholar 

  132. Taplin ME, Regan MM, Ko YJ, Bubley GJ, Duggan SE, Werner L et al. Phase II study of androgen synthesis inhibition with ketoconazole, hydrocortisone, and dutasteride in asymptomatic castration-resistant prostate cancer. Clin Cancer Res 2009; 15: 7099–7105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Drake CG . Prostate cancer as a model for tumour immunotherapy. Nat Rev Immunol 2010; 10: 580–593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Small EJ, Fratesi P, Reese DM, Strang G, Laus R, Peshwa MV et al. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol 2000; 18: 3894–3903.

    Article  CAS  PubMed  Google Scholar 

  135. Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH 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: 3089–3094.

    Article  CAS  PubMed  Google Scholar 

  136. Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L 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: 3670–3679.

    Article  CAS  PubMed  Google Scholar 

  137. Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M 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: 1099–1105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Hoos A, Eggermont AM, Janetzki S, Hodi FS, Ibrahim R, Anderson A et al. Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst 2010; 102: 1388–1397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Armstrong AJ, Garrett-Mayer E, de Wit R, Tannock I, Eisenberger M . Prediction of survival following first-line chemotherapy in men with castration-resistant metastatic prostate cancer. Clin Cancer Res 2010; 16: 203–211.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

    E S Antonarakis

  2. Department of Medicine, Duke Cancer Institute and the Duke Prostate Center, Duke University, Durham, NC, USA

    A J Armstrong

  3. Department of Surgery, Duke Cancer Institute and the Duke Prostate Center, Duke University, Durham, NC, USA

    A J Armstrong

Authors
  1. E S Antonarakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A J Armstrong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E S Antonarakis.

Ethics declarations

Competing interests

Dr Antonarakis declares no conflicts of interest. Dr Armstrong has served as a consultant for Novartis and Amgen; he is on the speaker's bureau for Pfizer, sanofi-aventis and Dendreon; and he has received research funding from Bristol-Myers Squibb, Imclone, Pfizer/Wyeth, Active Biotech, Medivation, Dendreon, Novartis and sanofi-aventis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Antonarakis, E., Armstrong, A. Evolving standards in the treatment of docetaxel-refractory castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 14, 192–205 (2011). https://doi.org/10.1038/pcan.2011.23

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/pcan.2011.23

Keywords

This article is cited by

Search

Advanced search

Quick links