Zielgerichtete Therapie für Patienten mit Schilddrüsenkarzinom

Zusammenfassung

Bislang waren die medikamentösen therapeutischen Optionen für Patienten mit metastasierten differenzierten (Radiojod-refraktären) oder medullären Schilddrüsenkarzinomen begrenzt. In den letzten Jahren wurden große Fortschritte gemacht, die genetischen Aberrationen, die für die Pathogenese dieser Tumoren ursächlich sind, zu erkennen und funktionell zu verstehen. Basierend auf diesen Erkenntnissen wurden neuere zielgerichtete Krebsmedikamente, sogenannte Kinase-Inhibitoren, für Patienten mit Schilddrüsenkarzinomen im Rahmen klinischer Studien evaluiert. Vor diesem Hintergrund wurde eine selektive Literaturrecherche der MEDLINE- und ASCO-Datenbanken durchgeführt und relevante Studien zu neueren medikamentösen Therapieansätzen bei Schilddrüsenkarzinomen in diesem Übersichtsartikel zusammengefasst. Insbesondere Inhibitoren, die die Signaltransduktion der VEGF-Rezeptorfamilie hemmen, zeigten in Phase-II-Studien bei Patienten mit differenzierten und medullären Schilddrüsenkarzinomen eine eindrucksvolle Wirksamkeit. In diesen Studien wurden objektive Remissionsraten von bis zu 35 % und Krankheitsstabilisierungsraten von weiteren 50 % beobachtet. Das mediane progressionsfreie Überleben lag zwischen 7 und 28 Monaten. Die Ergebnisse dieser Studien belegen, dass diese Kinase-Inhibitoren in der Behandlung von Schilddrüsenkarzinomen eine beachtliche Wirksamkeit aufweisen können. Dennoch sollte der klinische Nutzen dieser teilweise toxischen und kostenintensiven Therapien in Phase-III-Studien überprüft werden, bevor generelle Therapieempfehlungen ausgesprochen werden können.

Abstract

Therapeutic options for patients suffering from metastatic and radioiodine-refractory differentiated and/or medullary thyroid cancer are limited. The clinical benefit of classical chemotherapeutic agents is marginal. Recently, advantages have been made in understanding the molecular pathways that are involved in the pathogenesis of thyroid cancer. Against this background novel agents targeting oncogenic kinases involved in the pathogenesis of thyroid cancer have entered clinical trials. A selective search of Medline and ASCO databases has conducted to identify results of clinical trials using targeted agents for thyroid cancer. Promising results were reported for drugs targeting the VEGF receptor family. Significant clinical activity was observed in these trials with objective responses in 35 % and stable disease in an additional 50 % of patients. Median progression-free survival ranged from 7 to 28 months. These results demonstrate clinical activity of several targeted agents in patients with differentiated and/or medullary thyroid cancer. Further investigation of these agents in phase III trials is warranted.

Schlüsselwörter

Schilddrüsenkarzinom - zielgerichtete Therapie - Sorafenib - Sunitinib - Vandetanib - Pazopanib - Motesanib - Axitinib

Key words

thyroid cancer - targeted therapy - sorafenib - sunitinib - vandetanib - pazopanib - motesanib - axitinib

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