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Castration-resistant metastatic prostate cancer: current status and treatment possibilities

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  • New Trends in Clinical Oncology
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Abstract

Prostate cancer (PCa) is the most common cancer in the male population in Western countries, second to skin cancer. Hormonal therapy allows long-lasting and effective control of cancer-related symptoms in advanced stages; however, in almost all patients with metastatic PCa the disease will progress when it becomes castration-resistant (CRPC). Chemotherapy with docetaxel was a turning point in CRPC, as, for the first time, it resulted in an increased survival time in comparison with mitoxantrone and prednisone. Combination therapy with docetaxel and prednisone is the first-line treatment of choice. Once the cancer has progressed, there is no clear alternative, although some new agents have shown promise in the treatment of this type of cancer. This review will provide an overview of the current status of CRPC, including clinical status, prognosis, firstline treatment and new second-line treatment options.

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References

  1. Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  2. Cooperberg MR, Moul JW, Carroll PR (2005) The changing face of prostate cancer. J Clin Oncol 23:8146–8151

    Article  PubMed  Google Scholar 

  3. Uchio EM, Aslan M, Wells CK et al (2010) Impact of biochemical recurrence in prostate cancer among US veterans. Arch Intern Med 170:1390–1395

    Article  PubMed  Google Scholar 

  4. Eisenberger MA, Simon R, O’Dwyer PJ, Friedman HA (1985) A re-evaluation of nonhormonal cytotoxic chemotherapy in the treatment of prostatic carcinoma. J Clin Oncol 3:827–841

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. Tannock IF, de Wit R, Berry WR et al; on behalf of the TAX 327 Investigators (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351: 1502–1512

    Article  PubMed  CAS  Google Scholar 

  7. Petrylak DP, Tangen CM, Hussain MH et al (2004) Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351:1513–1520

    Article  PubMed  CAS  Google Scholar 

  8. Berry DL, Moinpour CM, Jiang CS et al (2006) Quality of life and pain in advanced stage prostate cancer: results of a Southwest Oncology Group randomized trial comparing docetaxel and estramustine to mitoxantrone and prednisone. J Clin Oncol 24:2828–2835

    Article  PubMed  CAS  Google Scholar 

  9. Rosenberg JE, Weinberg VK, Kelly WK et al (2007) Activity of second-line chemotherapy in docetaxel-refractory hormone-refractory prostate cancer patients: randomized phase 2 study of ixabepilone or mitoxantrone and prednisone. Cancer 110:556–563

    Article  PubMed  CAS  Google Scholar 

  10. Tannock IF, Osoba D, Stockler MR et al (1996) Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormoneresistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 14:1756–1764

    PubMed  CAS  Google Scholar 

  11. Scher HI, Halabi S, Tannock I et al (2008) Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26:1148–1159

    Article  PubMed  Google Scholar 

  12. Van Allen EM, Ryan CJ (2009) Novel secondary hormonal therapy in advanced prostate cancer: an update. Curr Opin Urol 19:315–321

    Article  PubMed  Google Scholar 

  13. Hotte SJ, Saad F (2001) Current management of castrate-resistant prostate cancer. Curr Oncol 17[Suppl 2]:S72–79

    Google Scholar 

  14. Scher HI, Kelly WK (1993) Flutamide withdrawal syndrome: its impact on clinical trials in hormone-refractory prostate cancer. J Clin Oncol 11:1566–1572

    PubMed  CAS  Google Scholar 

  15. Small EJ, Halabi S, Dawson NA et al (2004) Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALBG 9583). J Clin Oncol 22:1025–1033

    Article  PubMed  CAS  Google Scholar 

  16. Sartor AO, Tangen CM, Hussain MH et al (2008) Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426). Cancer 112:2393–2400

    Article  PubMed  CAS  Google Scholar 

  17. Suzuki H, Okihara K, Miyake H et al (2008) Nonsteroidal Antiandrogen Sequential Alternation for Prostate Cancer Study Group. Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade. J Urol 180:921–927

    Article  PubMed  CAS  Google Scholar 

  18. Hussain M, Wolf M, Marshall E et al (1994) Effects of continued androgen deprivation therapy and other prognostic factors on response and survival in phase II chemotherapy trials for hormonerefractory prostate cancer: a Southwest Oncology Group report. J Clin Oncol 12:1868–1875

    PubMed  CAS  Google Scholar 

  19. Oh WK, Kanthoff PW, Weinberg V et al (2004) Prospective, multicentre, randomized phase II trial of the herbal supplement PC-SPES and diethylbestrol in patients with androgen-independent prostate cancer. Clin Oncol 22:3705–3712

    Article  CAS  Google Scholar 

  20. Orlando M, Chacon A, Salum G, Chacon DR (2000) Low dose continuous oral fosfestrol is highly active in hormone refractory prostate cancer. Ann Oncol 11:177–181

    Article  PubMed  CAS  Google Scholar 

  21. Kantoff PW, Halabi S, Conaway M et al (1999) Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B9182 study. J Clin Oncol 17:2506–2513

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  23. Scher HI, Halabi S, Tannock I et al (2008) Design and end points of clinical trials for patients with progressive prostate cancer and castrate level of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26:1148

    Article  PubMed  Google Scholar 

  24. Scher HI, Warren M, Heller G (2007) The association between measures of progression and survival in castrate metastatic prostate cancer. Clin Cancer Res 13:1488–1492

    Article  PubMed  CAS  Google Scholar 

  25. Armstrong AJ, Garret-Mayer E, de Wit R et al (2010) Prediction of survival following first line chemotherapy in men with castration resistant metastatic prostate cancer. Clin Cancer Res 16: 203–211

    Article  PubMed  CAS  Google Scholar 

  26. Berthold DR, Pond GR, de Wit R et al (2008) Survival and PSA response of patients in the TAX 327 study who crossed over to receive docetaxel after mitoxantrone or vice versa. Ann Oncol 19:1749–1753

    Article  PubMed  CAS  Google Scholar 

  27. Fontana A, Galli L, Fioravanti A et al (2009) Clinical and pharmacodynamic evaluation of metronomic cyclophosphamide, celecoxib and dexamethasone in advanced hormone-refractory prostate cancer. Clin Cancer Res 15:4954–4962

    Article  PubMed  CAS  Google Scholar 

  28. Sternberg CN (2007) Satraplatin demonstrates a significant clinical benefit in patients with hormone-refractory prostate cancer. Proc Am Soc Clin Oncol

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

    Article  CAS  Google Scholar 

  30. Bissery M-C (2001) Preclinical evaluation of new taxoids. Curr Pharm Des 7:1251–1257

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  32. FDA Center for Drug Evaluation and Research. Approval Package for: Jevtana. June 17, 2010. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/201023s000Approv. pdf. Accessed February 2, 2011

  33. de Bono JS, Logothetis CJ, Molina A et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364:1995–2005

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  36. Chi KN, Hotte SJ, Yu EY et al (2010) Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer. J Clin Oncol 28:4247–4254

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  38. Fizazi K, Carducci M, Smith M et al (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377:813–822

    Article  PubMed  CAS  Google Scholar 

  39. Sonpavde G, Sternberg CN (2011) Contemporary management of metastatic castration-resistant prostate cancer. Curr Opin Urol 21:241–247

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Servicio de Oncología, Instituto de Oncología de la Vall d’Hebron, Barcelona, Spain

    Joan Carles

  2. Servicio de Oncología, Hospital Universitario 12 de Octubre, Madrid, Spain

    Daniel Castellano

  3. Servicio de Oncología, Instituto Valenciano de Oncología, Valencia, Spain

    Miguel Ángel Climent

  4. Servicio de Oncología, Hospital de Sant Pau, Barcelona, Spain

    Pablo Maroto

  5. Servicio de Urología, Hospital Universitario Virgen del Rocío, Sevilla, Spain

    Rafael Medina

  6. Servicio de Urología IDIBAPS, Hospital Clínic de Barcelona, Barcelona, Spain

    Antonio Alcaraz

  7. Departamento de Oncología, Hospital General Vall d’Hebron, Passeig Vall d’Hebron, 119-129, ES-08035, Barcelona, Spain

    Joan Carles

Authors
  1. Joan Carles
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  2. Daniel Castellano
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  3. Miguel Ángel Climent
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  4. Pablo Maroto
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  5. Rafael Medina
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  6. Antonio Alcaraz
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Correspondence to Joan Carles.

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Supported by an unrestricted educational grant from MSD Oncology

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Carles, J., Castellano, D., Climent, M.Á. et al. Castration-resistant metastatic prostate cancer: current status and treatment possibilities. Clin Transl Oncol 14, 169–176 (2012). https://doi.org/10.1007/s12094-012-0780-8

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  • DOI: https://doi.org/10.1007/s12094-012-0780-8

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