Zusammenfassung
Solitär Zytokin-basierte Behandlungskonzepte sind aufgrund des reduzierten klinischen Ansprechens und der viel versprechenden Daten zur molekularen Targeted-Therapie beim metastasierten Nierenzellkarzinom (NZK) mittlerweile nicht mehr uneingeschränkt als primäre Therapie empfohlen. Seit der Einführung der sog. Targeted-Therapien beim fortgeschrittenen Nierenkarzinom sind eine Vielzahl an mittlerweile randomisierten kontrollierten prospektiven Studien durchgeführt worden. Substantielle und zulassungsrelevante Daten liegen für die Multikinaseinhibitoren Sorafenib (Nexavar®) und Sunitinib (Sutent®), den mTOR-Inhibitor-Temsirolimus (Torisel®) und den monoklonalen Antikörper Bevacizumab (Avastin®) in Kombination mit Interferon-α vor.
In Deutschland sind Sunitinib, Temsirolimus und Bevacizumab als Erstlinientherapie zugelassen, Sorafenib erhielt die Zulassung als Zweitlinientherapie. In klinischen Studien werden derzeit die Fragestellungen nach dem optimalen Zeitpunkt, der neoadjuvanten und adjuvanten Wertigkeit sowie der Art und Sequenz der molekular ausgerichteten Therapie untersucht. Experimentelle Untersuchungen zum besseren Verständnis der Signalwege werden möglichst in Zukunft eine molekulare Präselektion und ggf. individualisierte Therapie beim metastasierten NZK ermöglichen. Ziel der vorliegenden Arbeit ist es, die für die Targeted-Therapeutika in der Behandlung des metastasierten NZK zur Verfügung stehenden klinischen Daten darzustellen und kritisch zu interpretieren.
Abstract
Therapeutic approaches based solely on cytokine are meanwhile no longer recommended without restrictions as the primary therapy for metastatic renal cancer due to the reduced clinical response and the promising available data regarding molecular therapy. Several randomized controlled studies have been performed since the introduction of the so-called targeted therapies for metastatic renal cancer. Substantial data relevant for drug approval are available for the multikinase inhibitors sorafenib (Nexavar®) and sunitinib (Sutent®), the mTOR inhibitor temsirolimus (Torisel®), and the monoclonal antibody bevacizumab (Avastin®) in combination with interferon-α. Sunitinib, temsirolimus, and bevacizumab are approved for first-line treatment, whereas sorafenib was approved for second-line treatment in Germany.
Clinical trials are currently investigating the questions of optimal timing, value of neoadjuvant or adjuvant treatment, form, and sequence of the molecular targeted therapy. Experimental investigations for a better understanding of signaling pathways will preferably allow preselecting patients for an individualized therapy in metastatic renal cell cancer (RCC). The aim of the present paper is to address and to critically discuss the clinical data that are currently available regarding“targeted” therapeutics during the treatment of metastatic RCC.
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Der korrespondierende Autor weist auf folgende Beziehung hin: Advisory Board Mitglied der Firma Bayer und Pfizer. Trotz des möglichen Interessenkonflikts ist der Beitrag unabhängig und produktneutral.
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Merseburger, A., Kuczyk, M. Der Stellenwert der Targeted-Therapie beim Nierenzellkarzinom. Urologe 47, 1303–1310 (2008). https://doi.org/10.1007/s00120-008-1746-x
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DOI: https://doi.org/10.1007/s00120-008-1746-x