Innovative zielgerichtete Therapie des fortgeschrittenen Nierenzellkarzinoms

Zusammenfassung

Das Nierenzellkarzinom ist das dritthäufigste und nach wie vor tödlichste urologische Malignom; seine Inzidenz ist in den letzten 40 Jahren signifikant angestiegen. Etwa jeder zweite Patient entwickelt entweder zeitnah zur Primärdiagnose oder metachron Metastasen seiner Tumorerkrankung. Durch das zunehmende Verständnis genetischer Alterationen bzw. dysfunktionaler Signaltransduktionswege der verschiedenen Nierenzellkarzinomsubtypen wurde in den letzten Jahren die Entwicklung von innovativen zielgerichteten Therapeutika möglich. Mit Hilfe dieser Substanzen, die insbesondere den VEGF- und mTOR-Signaltransduktionsweg blockieren, wurden die Behandlungsstrategien des fortgeschrittenen Nierenzellkarzinoms revolutioniert, das mittlere Gesamtüberleben hat sich innerhalb weniger Jahre mindestens verdoppelt. Dieser Übersichtsartikel diskutiert die derzeit aktuellen klinischen Studienergebnisse zu den zur Verfügung stehenden Substanzen, die Wertigkeit ihres präoperativen, adjuvanten, sequenziellen und kombinierten Einsatzes.

Summary

Renal cell carcinoma (RCC) is a common urologic tumour and accounts for about 3 % of all human malignancies; its incidence has increased steadily in recent decades. The annual mortality-to-incidence ratio with RCC is significantly higher compared to other urological malignancies. It is estimated that approximately 25–30 % of all patients with RCC have metastases at presentation, and even following complete resection of the primary tumour by radical or partial nephrectomy, relapse occurs in 20–30 % of patients. Only recently, the discovery of specific genetic alterations as well as distinct dysfunctional signal transduction pathways in the different renal cell carcinoma subtypes has enabled the development of innovative targeted drugs. Particularly those targeting the VEGF- and mTOR-pathways revolutionized the treatment of advanced renal cancer; in fact, the median tumour specific overall survival could be at least doubled in only a few years. This review discusses current data on clinical trials evaluating these innovative drugs with focus on their efficacy in the adjuvant and neoadjuvant setting as well as their sequential and combined application.

Schlüsselwörter

Nierenzellkarzinom - zielgerichtete Therapie - Nephrektomie - Metastasen - adjuvante Therapie

Keywords

renal cell carcinoma - target therapy - nephrectomy - metastasis - adjuvant therapy

Literatur

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