Aktuelle Urol 2015; 46(01): 59-65
DOI: 10.1055/s-0034-1395655
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Kastrationsresistentes Prostatakarzinom 2015

Castration Resistant Prostate Cancer 2015
A. S. Merseburger
1   Klinik für Urologie und Urologische Onkologie, Medizinische Hochschule Hannover, Hannover
,
A. Böker
1   Klinik für Urologie und Urologische Onkologie, Medizinische Hochschule Hannover, Hannover
,
M. A. Kuczyk
1   Klinik für Urologie und Urologische Onkologie, Medizinische Hochschule Hannover, Hannover
,
C.-A. von Klot
1   Klinik für Urologie und Urologische Onkologie, Medizinische Hochschule Hannover, Hannover
› Author Affiliations
Further Information

Publication History

Publication Date:
06 February 2015 (online)

Zusammenfassung

Die Prostatakarzinomerkrankung ist nach wie vor die häufigste urologische Krebserkrankung des älteren Mannes. Bei einigen Patienten entsteht ein metastasiertes Prostatakarzinom welches mit antiandrogener Therapie palliativ über Jahre in einem stabilen Krankheitsgeschehen verlaufen kann. Im Mittel nach 3–4 Jahren entwickeln die betroffenen Männer einen erneuten PSA- und Krankheitsprogress mit der Ausbildung eines sogenannten kastrationsresistenten Tumorleidens. Bis vor 5 Jahren war die zytotoxische Chemotherapie mit Docetaxel die einzige lebensverlängernde Therapieoption in dieser Situation. In den letzten 5 Jahren haben die Ergebnisse von randomisierten Phase III Studien zur Zulassung von 5 neuen Wirkstoffen zur Behandlung des metastasierten kastrationsresistenten Prostatakarzinoms (mCRPC) geführt. Die Ergebnisse und Zulassungssituation der Substanzen, Abirateron, Enzalutamid, Cabazitaxel, Sipuleucel-T und des Radium-223 werden im Nachfolgenden beschrieben. Zudem werden Aspekte der Sequenztherapie und mögliche molekulare Zukunftsansätze diskutiert.

Abstract

Prostate cancer is still the most common urological cancer of the elderly man. In some patients, a metastatic prostate cancer arises which may remain a stable disease for years with palliative antiandrogen therapy. On average, after 3–4 years, affected men develop a PSA rise and disease progression with the formation of a so-called castration-resistant disease. 5 years ago cytotoxic chemotherapy with docetaxel was the only life-prolonging treatment option in this situation. In the last 5 years, the results of randomised phase III studies have led to the approval of 5 new agents for the treatment of metastatic castration resistant prostate cancer (mCRPC). The results and approval status of the substances, Abiraterone, Enzalutamide, Cabazitaxel, Sipuleucel-T and radium-223 are described below. In addition, some aspects of sequential therapy and possible future molecular approaches are discussed.

 
  • Literatur

  • 1 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. ASCO Meeting Abstracts 2014; 32 LBA2
  • 2 Heidenreich A, Bastian PJ, Bellmunt J et al. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 2014; 65: 467
  • 3 Merseburger AS, Kuczyk MA, Wolff JM. Pathophysiology and therapy of castration-resistant prostate cancer. Urologe A 2013; 52: 219
  • 4 Merseburger AS, Bellmunt J, Jenkins C et al. Perspectives on treatment of metastatic castration-resistant prostate cancer. Oncologist 2013; 18: 558
  • 5 Sridhar SS, Freedland SJ, Gleave ME et al. Castration-resistant prostate cancer: from new pathophysiology to new treatment. Eur Urol 2014; 65: 289
  • 6 Korpal M, Korn JM, Gao X et al. An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide). Cancer Discov 2013; 3: 1030
  • 7 von Klot CA, Kramer MW, Boker A et al. Is there an anti-androgen withdrawal syndrome for enzalutamide?. World J Urol 2014; 32: 1171
  • 8 Scher HI, Fizazi K, Saad F et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012; 367: 1187
  • 9 Merseburger AS, Scher HI, Bellmunt J et al. Enzalutamide in European and North American men participating in the AFFIRM trial. BJU Int 2014;
  • 10 Beer TM, Armstrong AJ, Rathkopf DE et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 2014; 371: 424
  • 11 Fizazi K, Scher HI, Molina A et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2012; 13: 983
  • 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
  • 13 Janssen-CilagGmbH: Dossier zur Nutzenbewertung gemäß § 35a SGB V: Abirateronacetat, Modul 4 A., Stand 14.01.2013
  • 14 Ryan CJ, Fizazi K, Miller K et al. Final overall survival (OS) analysis of COU-AA-302, a randomized phase 3 study of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) without prior chemotherapy. Presented at the ESMO, Madrid 2014;
  • 15 Berthold DR, Pond GR, Soban F et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 2008; 26: 242
  • 16 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
  • 17 Heidenreich A, Pfister D, Merseburger A et al. Castration-resistant prostate cancer: where we stand in 2013 and what urologists should know. Eur Urol. 2013 64. 260
  • 18 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
  • 19 Heidenreich A, Scholz HJ, Rogenhofer S et al. Cabazitaxel plus prednisone for metastatic castration-resistant prostate cancer progressing after docetaxel: results from the German compassionate-use programme. Eur Urol 2013; 63: 977
  • 20 Kantoff PW, Higano CS, Shore ND et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363: 411
  • 21 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
  • 22 Sartor O, Coleman R, Nilsson S et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol 2014; 15: 738
  • 23 De Wit R, Fizazi K, Jinga V et al. Phase 3, randomized, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients (pts) with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) (ELM-PC 4 trial). ASCO Meeting Abstracts 2014; 32: 5008
  • 24 Dreicer R, Jones R, Oudard S et al. Results from a phase 3, randomized, double-blind, multicenter, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy (ELM-PC 5 trial). ASCO Meeting Abstracts 2014; 32: 7
  • 25 Smith MR, Sweeney CJ, Corn PG et al. Cabozantinib in Chemotherapy-Pretreated Metastatic Castration-Resistant Prostate Cancer: Results of a Phase II Nonrandomized Expansion Study. J Clin Oncol 2014;
  • 26 Saad F, Hotte S, North S et al. Randomized phase II trial of Custirsen (OGX-011) in combination with docetaxel or mitoxantrone as second-line therapy in patients with metastatic castrate-resistant prostate cancer progressing after first-line docetaxel: CUOG trial P-06c. Clin Cancer Res 2011; 17: 5765
  • 27 Clegg NJ, Wongvipat J, Joseph JD et al. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res 2012; 72: 1494
  • 28 Foster WR, Car BD, Shi H et al. Drug safety is a barrier to the discovery and development of new androgen receptor antagonists. Prostate 2011; 71: 480
  • 29 Rathkopf DE, Morris MJ, Fox JJ et al. Phase I study of ARN-509, a novel antiandrogen, in the treatment of castration-resistant prostate cancer. J Clin Oncol 2013; 31: 3525
  • 30 Armstrong AJ, Haggman M, Stadler WM et al. Long-term survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castration-resistant prostate cancer. Clin Cancer Res 2013; 19: 6891
  • 31 Reuter CW, Morgan MA, Grunwald V et al. Salvage chemotherapy with carboplatin plus weekly docetaxel in patients (pts) with castration- and docetaxel-resistant prostate cancer (DRPC): Associations of patient and disease characteristics with overall survival (OS). ASCO Meeting Abstracts 2014; 32: 75
  • 32 Merseburger AS, Hammerer P, Rozet F et al. Androgen deprivation therapy in castrate-resistant prostate cancer: how important is GnRH agonist backbone therapy?. World J Urol 2014;
  • 33 Small EJ, Youngren J, Beer TM et al. The molecular and pathway characterization of patients with metastatic castration resistant prostate cancer (mCRPC) refractory to therapy with abiraterone acetate or enzalutamide: Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT). ASCO Meeting Abstracts 2014; 32: 79
  • 34 Manni A, Bartholomew M, Caplan R et al. Androgen priming and chemotherapy in advanced prostate cancer: evaluation of determinants of clinical outcome. J Clin Oncol 1988; 6: 1456
  • 35 Pinski J, Xiong S, Wang Q et al. Effect of luteinizing hormone on the steroidogenic pathway in prostate cancer. Prostate 2011; 71: 892
  • 36 Schweizer MT, Zhou XC, Wang H et al. The Influence of Prior Abiraterone Treatment on the Clinical Activity of Docetaxel in Men with Metastatic Castration-resistant Prostate Cancer. Eur Urol 2014; 66: 646
  • 37 Antonarakis ES, Lu C, Wang H et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 2014; 371: 1028