Skip to main content
SpringerLink
Log in

Rolle der Chemotherapie beim kastrationsresistenten Prostatakarzinom

Gibt es neue Ansätze?

Role of chemotherapy in castration-resistant prostate cancer

Are there new approaches?

  • Leitthema
  • Published:
Der Urologe Aims and scope Submit manuscript

Zusammenfassung

Chemotherapieoptionen in der Behandlung des metastasierten kastrationsresistenten Prostatakarzinoms (CRPC) waren bis vor kurzem sehr limitiert. Mitoxantron war in den 1990er Jahren aufgrund seiner palliativen Wirksamkeit zugelassen worden. Erst mit der Einführung von Docetaxel brachen neue Zeiten in der Therapie des CRPC an. Prednison und Docetaxel alle 3 Wochen zeigten einen Overall-survival- (OS-)Benefit gemeinsam mit einer Verbesserung der Lebensqualität und einer Schmerzreduktion. Weitere chemotherapeutische Therapiestrategien sind eine Reinduktion mit Docetaxel nach Ansprechen auf die Erstlinientherapie. Cabazitaxel, ein neu entwickelter semisynthetisch hergestellter Mikrotubulusinhibitor, wurde vor kurzem für die Behandlung des CRPC nach Docetaxel zugelassen. Dieser Überblicksartikel soll durch die Chemotherapieoptionen führen und eine Hilfestellung für die Optimierung der Chemotherapien im klinischen Alltag geben.

Abstract

Chemotherapy options for the treatment of metastatic castration-resistant prostate cancer (CRPC) have been very limited for many decades. Until 2004, only mitoxantrone was approved, providing palliation, but no survival benefit. With the introduction of docetaxel, the landscape of chemotherapy for CRPC changed substantially. Prednisone and three-weekly docetaxel showed an overall survival (OS) benefit compared to mitoxantrone plus prednisone, in addition to a significant improvement of quality of life and pain reduction. Further strategies to treat CRPC with chemotherapy include reinduction with docetaxel in responding patients and the use of cabazitaxel, a novel semi-synthetic microtubule inhibitor, in the docetaxel-refractory population. This review article is meant to guide physicians through the optimal use of chemotherapy in CRPC patients in daily clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Anderson J, Van Poppel H, Bellmunt J et al (2007) Chemotherapy for older patients with prostate cancer. BJU Int 99:269–273

    Article  PubMed  Google Scholar 

  2. Armstrong AJ, Garrett-Mayer E, Ou Yang YC et al (2007) Prostate-specific antigen and pain surrogacy analysis in metastatic hormone-refractory prostate cancer. J Clin Oncol 25:3965–3970

    Article  PubMed  Google Scholar 

  3. Armstrong AJ, Garrett-Mayer ES, Yang YC et al (2007) A contemporary prognostic nomogram for men with hormone-refractory metastatic prostate cancer: a TAX327 study analysis. Clin Cancer Res 13:6396–6403

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  5. Bauer JJ, Sesterhenn IA, Mostofi FK et al (1996) Elevated levels of apoptosis regulator proteins p53 and bcl-2 are independent prognostic biomarkers in surgically treated clinically localized prostate cancer. J Urol 156:1511–1516

    Article  PubMed  CAS  Google Scholar 

  6. Berthold DR, Pond GR, Soban F et al (2008) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 26:242–245

    Article  PubMed  CAS  Google Scholar 

  7. 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 

  8. Chin SN, Wang L, Moore M, Sridhar SS (2010) A review of the patterns of docetaxel use for hormone-resistant prostate cancer at the Princess Margaret Hospital. Curr Oncol 17:24–29

    PubMed  CAS  Google Scholar 

  9. Chittoor S, Berry W, Loesch D et al (2006) Phase II study of low-dose docetaxel/estramustine in elderly patients or patients aged 18–74 years with hormone-refractory prostate cancer. Clin Genitourin Cancer 5:212–218

    Article  PubMed  CAS  Google Scholar 

  10. Dahut WL, Gulley JL, Arlen PM et al (2004) Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer. J Clin Oncol 22:2532–2539

    Article  PubMed  CAS  Google Scholar 

  11. Bono JS de, 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 

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

    Article  PubMed  Google Scholar 

  13. Droz JP, Balducci L, Bolla M et al (2010) Management of prostate cancer in older men: recommendations of a working group of the International Society of Geriatric Oncology. BJU Int 106:462–469

    Article  PubMed  Google Scholar 

  14. Gan L, Chen S, Wang Y et al (2009) Inhibition of the androgen receptor as a novel mechanism of taxol chemotherapy in prostate cancer. Cancer Res 69:8386–8394

    Article  PubMed  CAS  Google Scholar 

  15. Greenberger LM, Sampath D (2006) Resistance to taxanes. In: Teicher BA (Hrsg) Cancer drug discovery and development: cancer drug resistance. Humana, Totowa, pp 329–358

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

    PubMed  CAS  Google Scholar 

  17. Heidenreich A, Bolla M, Joniau S et al (2011) EAU guidelines on prostate cancer. EAU Guidelines, http://www.uroweb.com

  18. Higano CS (2011) New treatment options for patients with metastatic castration-resistant prostate cancer. Cancer Treat Rev (Epub ahead of print)

  19. Kelly WK, Halabi S, Carducci MA et al (2010) 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 28(Suppl):18

    Google Scholar 

  20. Lee DJ, Cha EK, Dubin JM et al (2011) Novel therapeutics for the management of castration-resistant prostate cancer (CRPC). BJU Int (Epub ahead of print)

  21. Luedecke G, Hauptmann A, Koehler E, Weidner W (2007) Optimized palliative care in hormone refractory prostate cancer (HRPC) patients in advanced age by low dose Taxotere therapy and intermittent application. 22nd Annual EAU Congress 2007, S 310

  22. Luedecke G, Hauptmann A, Koehler E, Weidner W (2007) Optimized palliative care in hormone refractory prostate cancer (HRPC) patients in advanced age: Four years of uro-oncological experiences in ambulant docetaxel chemotherapy. 2007 Prostate Cancer Symposium, S 255

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

    Article  PubMed  CAS  Google Scholar 

  24. Navone NM, Troncoso P, Pisters LL et al (1993) p53 protein accumulation and gene mutation in the progression of human prostate carcinoma. J Natl Cancer Inst 85:1657–1669

    Article  PubMed  CAS  Google Scholar 

  25. Nelius T, Klatte T, Riese W de, Filleur S (2008) Impact of PSA flare-up in patients with hormone-refractory prostate cancer undergoing chemotherapy. Int Urol Nephrol 40:97–104

    Article  PubMed  CAS  Google Scholar 

  26. Petrylak DP, Ankerst DP, Jiang CS et al (2006) Evaluation of prostate-specific antigen declines for surrogacy in patients treated on SWOG 99–16. J Natl Cancer Inst 98:516–521

    Article  PubMed  Google Scholar 

  27. 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 

  28. Pivot X, Koralewski P, Hidalgo JL et al (2008) A multicenter phase II study of XRP6258 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients. Ann Oncol 19:1547–1552

    Article  PubMed  CAS  Google Scholar 

  29. Pond GR, Armstrong AJ, Wood BA et al (2011) Evaluating the value of continuing docetaxel and prednisone (DP) beyond 10 cycles in men with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 29(Suppl):4582

    Google Scholar 

  30. Repetto L, Fratino L, Audisio RA et al (2002) Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol 20:494–502

    Article  PubMed  Google Scholar 

  31. Riou JF, Naudin A, Lavelle F (1992) Effects of Taxotere on murine and human tumor cell lines. Biochem Biophys Res Commun 187:164–170

    Article  PubMed  CAS  Google Scholar 

  32. Robinson D, Sandblom G, Johansson R et al (2008) PSA kinetics provide improved prediction of survival in metastatic hormone-refractory prostate cancer. Urology 72:903–907

    Article  PubMed  Google Scholar 

  33. Scher HI, Jia X, Chi K et al (2011) Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer. J Clin Oncol 29:2191–2198

    Article  PubMed  CAS  Google Scholar 

  34. Seruga B, Horgan AM, Pond GR et al (2011) Tolerability and efficacy of chemotherapy in older men with metastatic castrate-resistant prostate cancer (mCRPC) in the TAX 327 trial. J Clin Oncol 29(Suppl):4530

    Google Scholar 

  35. Stapleton AM, Timme TL, Gousse AE et al (1997) Primary human prostate cancer cells harboring p53 mutations are clonally expanded in metastases. Clin Cancer Res 3:1389–1397

    PubMed  CAS  Google Scholar 

  36. Sternberg CN, Dumez H, Van Poppel H et al (2009) Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer. Ann Oncol 20:1264–1269

    Article  PubMed  CAS  Google Scholar 

  37. Sternberg CN, Krainer M, Oh WK et al (2007) The medical management of prostate cancer: a multidisciplinary team approach. BJU Int 99:22–27

    Article  PubMed  CAS  Google Scholar 

  38. Tannock IF, Wit R de, Berry WR et al (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502–1512

    Article  PubMed  CAS  Google Scholar 

  39. Tannock IF, Osoba D, Stockler MR et al (1996) 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 14:1756–1764

    PubMed  CAS  Google Scholar 

  40. Theodorescu D, Broder SR, Boyd JC et al (1997) p53, bcl-2 and retinoblastoma proteins as long-term prognostic markers in localized carcinoma of the prostate. J Urol 158:131–137

    Article  PubMed  CAS  Google Scholar 

  41. Tomioka S, Shimbo M, Amiya Y et al (2007) Significance of prostate-specific antigen-doubling time on survival of patients with hormone refractory prostate cancer and bone metastasis: analysis on 56 cases of cancer-specific death. Int J Urol 14:123–127

    Article  PubMed  CAS  Google Scholar 

Download references

Interessenskonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: M. De Santis Honorare für Beratungstätigkeit (Advisory Boards): Amgen, Bayer, Dendreon, Eli Lilly, GSK, Janssen Cilag, Novartis, Pfizer, Pierre-Fabre Oncology, Roche, Sanofi Aventis, Astellas, OncoGenix/Teva.

M. Bachner Honorare (speaker’s fees): Novartis, Takeda.

Author information

Authors and Affiliations

  1. 3. Medizinische Abteilung, Zentrum für Onkologie und Hämatologie, Angewandte Krebsforschung – Institution für Translationale Forschung Wien (ACR-ITR VIEnna), Kaiser Franz Josef-Spital – SMZ Süd, Kundratstraße 3, A-1100, Wien, Österreich

    M. De Santis & M. Bachner

Authors
  1. M. De Santis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Bachner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. De Santis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Santis, M., Bachner, M. Rolle der Chemotherapie beim kastrationsresistenten Prostatakarzinom. Urologe 51, 39–43 (2012). https://doi.org/10.1007/s00120-011-2739-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00120-011-2739-8

Schlüsselwörter

Keywords

Search

Navigation