Aktuelle Systemtherapie des metastasierten Prostatakarzinoms

Zusammenfassung

Das fortgeschrittene, metastasierte Prostatakarzinom erfordert eine systemische Therapie. Diese besteht bei Erstdiagnose aus einer Androgendeprivationstherapie mit dem Ziel der Absenkung des Testosteronwerts auf Kastrationsniveau und kann bei Patienten mit hoher Metastasenlast im hormonsensiblen Stadium initial durch eine Chemotherapie mit Docetaxel ergänzt werden. Wenn es zu einer Tumorprogression unter Androgendeprivationstherapie trotz Testosteronwerten im Kastrationsbereich kommt, spricht man von einem kastrationsresistenten Prostatakarzinom. Vor dem Hintergrund sich rasch entwickelnder neuer Therapieoptionen im kastrationsresistenten Stadium – darunter Abirateron, Enzalutamid, Cabazitaxel, Radium-223-Dichlorid – müssen bei der Auswahl einer geeigneten Substanz Zulassungskriterien und Nebenwirkungsprofil beachtet werden. Der folgende Artikel gibt einen Überblick über aktuelle Therapieoptionen zur Systemtherapie im hormonsensiblen und kastrationsresistenten Stadium des metastasierten Prostatakarzinoms.

Abstract

In patients with advanced, metastastic prostate cancer systemic therapy is indicated. At initial diagnosis, these patients are treated with androgen-deprivation therapy in order to lower androgen-levels at castration-level. This treatment initially can be combined with docetaxel chemotherapy, especially in patients with higher tumor burden. If prostate cancer progresses despite adequate castration level of androgens, we speak of castration-resistant prostate cancer. In the background of rapidly evolving new treatment options for castration-resistant prostate cancer – namely abiraterone, enzalutamide, cabzitaxel, radium-223-dichloride – the approval criteria and side-effect profile have to be taken into account. The following article summarizes curent systemic treatment options for metastatic hormone-naïve and castration-resistant prostate cancer.

Schlüsselwörter

metastasiertes kastrationsresistentes Prostatakarzinom - Docetaxel - Abirateron - Enzalutamid - Cabazitaxel - Radium-223-Dichlorid - Hormonchemotherapie

Key words

metastatic castration-resistant prostate cancer - docetaxel - abiraterone - enzalutamide - cabzitaxel - radium-223-dichloride - chemohormonal therapy

• Literatur

• 1 Beer TM, Armstrong AJ, Rathkopf DE et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014; 371: 424-433
• 2 de Bono JS, Logothetis CJ, Molina A et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011; 364: 1995-2005
• 3 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: 1147-1154
• 4 Di Lorenzo G, Buonerba C, Faiella A et al. Phase II study of docetaxel re-treatment in docetaxel-pretreated castration-resistant prostate cancer. BJU Int 2011; 107: 234-239
• 5 Heck MM, Thalgott M, Retz M et al. Rational indication for docetaxel rechallenge in metastatic castration-resistant prostate cancer. BJU Int 2012;
• 6 Heidenreich A, Bastian PJ, Bellmunt J et al. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. 2014;
• 7 Kellokumpu-Lehtinen P-L, Harmenberg U, Joensuu T et al. 2-Weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial. Lancet Oncol 2013; 14: 117-124
• 8 Parker C, Coleman RE, Nilsson S et al. Updated survival, quality of life (QOL) and safety data of radium-223 chloride (ra-223) in patients with castration-resistant prostate cancer (CRPC) with bone metastases from the phase 3 double-blind, randomized, multinational study (ALSYMPCA). Jahreskongress der Europäischen Gesellschaft für Onkologie (ESMO) 2012 2012;
• 9 Parker C, Nilsson S, Heinrich D et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013; 369: 213-223
• 10 Petrylak DP, Tangen CM, Hussain MHA et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004; 351: 1513-1520
• 11 Ryan CJ, Smith MR, Fizazi K, Miller K Final overall survival (OS) analysis of COU-AA-302, a randomized phase 3 study of abiraterone acetate acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) patients without prior chemotherapy. 39th ESMO 2014. Abstract 7530
• 12 Ryan CJ, Smith MR, de Bono JS et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013; 368: 138-148
• 13 Scher HI, Fizazi K, Saad F et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012; 367: 1187-1197
• 14 Sweeney C, Chen Y-H, Carducci MA et al. Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): An ECOG-led phase III randomized trial. J Clin Oncol 2014; 32: 5s (suppl; abstr LBA2)
• 15 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: 1502-1512