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Neue Therapiekonzepte des kastrationsrefraktären Prostatakarzinoms

Zwischen Hormonmanipulation, Target- und Chemotherapie

New therapy concepts for castration-resistant prostate cancer

Between hormone manipulation, targeted therapy and chemotherapy

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Zusammenfassung

Innerhalb der letzten beiden Jahre haben sich die therapeutischen Optionen des kastrationsrefraktären Prostatakarzinoms (CRPC) grundsätzlich geändert. Während in den letzten 10 Jahren nur durch die Chemotherapie mit Docetaxel ein Überlebensvorteil für die Patienten mit CRPC erzielt werden konnte, stehen uns mittlerweile 4 zugelassene Medikamente in dieser Indikation zur Verfügung und für das Immuntherapeutikum Sipuleucel-T wird mit einer Zulassung gerechnet. Docetaxel hat nach wie vor seinen festen Stellenwert in der Therapie des CRPC, stellt allerdings auch eine Zäsur in der zeitlichen Abfolge der einzelnen therapeutischen Optionen dar. Für Patienten mit asymptomatischem oder minimal symptomatischem CRPC vor einer Chemotherapie konnte ein signifikanter Überlebensvorteil durch die Therapie mit dem Androgenbiosyntheseinhibitor Abirateron verzeichnet werden. Daten für das Antiandrogen Enzalutamid in dieser Indikationsstellung werden in Kürze erwartet. Für Patienten nach Docetaxel-Versagen konnten Abirateron, Enzalutamid und Cabazitaxel einen Überlebensvorteil in Phase-III-Studien zeigen. Mit Alpharadin steht uns ein Radionuklid nur Verfügung, das nicht nur zu einer Palliation von Knochenmetastasen assoziierten Beschwerden führt, sondern auch zu einem Überlebensvorteil von CRPC-Patienten beiträgt. In diesem Review sollen die einzelnen Substanzen in Hinblick auf Wirkmechanismus, Studienergebnisse und Indikationsstellung beleuchtet werden und ein Ausblick auf neue Therapieoptionen wie einer Target-Therapie mit dem Tyrosinkinaseinhibitor Cabozantinib oder einer Immuntherapie mit Sipuleucel-T oder Prostvac gegeben werden.

Abstract

Within the last 2 years the therapeutic landscape of castration-resistant prostate cancer (CRPC) has dramatically changed. While chemotherapy with docetaxel has only shown a survival benefit in CRPC patients in the last 10 years, in the meantime 4 approved drugs are available for this indication and approval for immunotherapy with sipuleucel-T is expected. Docetaxel still plays a significant role in the treatment of CRPC but is also a cesura in the therapeutic sequence. For asymptomatic or minimally symptomatic, chemotherapy naive CRPC patients a significant survival benefit was shown for treatment with the androgen biosynthesis inhibitor abiraterone. Clinical data for the antiandrogen enzalutamide are expected shortly for this indication. For patients where docetaxel has failed abiraterone, enzalutamide and cabazitaxel have shown survival benefits in phase III trials. The radionuclide alpharadin not only palliated morbidity induced by bone metastases but also prolonged survival of CRPC patients. This review deals with the various drugs with respect to mode of action, clinical results and indications and will focus on new treatment options, such as targeted therapy with cabozantinib or immunotherapy with sipuleucel-T and prostvac.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. K. Miller hat im Hinblick auf die Publikation Beziehung zu folgenden Firmen: Amgen, Astellas, Bayer, Dendreon, Janssen-Cilag, Novartis. H. Kübler hat in diesem Bezug folgende Firmen zu nennen: Astellas, Bayer, Sanofi-Aventis, Jannsen-Cilag. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Urologische Klinik und Poliklinik, Klinikum rechts der Isar, Technischen Universität München, Ismaninger Straße 22, 81675, München, Deutschland

    H. Kübler & K. Miller

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Correspondence to H. Kübler.

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Kübler, H., Miller, K. Neue Therapiekonzepte des kastrationsrefraktären Prostatakarzinoms. Urologe 52, 1517–1528 (2013). https://doi.org/10.1007/s00120-013-3247-9

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