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Laryngorhinootologie 2012; 91(S 01): S23-S143
DOI: 10.1055/s-0031-1297244
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© Georg Thieme Verlag KG Stuttgart · New York

Systemische Therapiestrategien bei Kopf-Hals-Karzinomen

Eine StandortbestimmungSystemic Therapy Strategies for Head-Neck Carcinomas: Current Status
T. K. Hoffmann
1   Hals-Nasen-Ohrenklinik, Universitätsklinikum Essen (Direktor: Prof. Dr. S. Lang)
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Publication History

Publication Date:
28 March 2012 (online)

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Zusammenfassung

Kopf-Hals-Karzinome, mehrheitlich plattenepithelialer Art, besitzen trotz intensiver Lokalbehandlung eine unbefriedigende Prognose. Zurückzuführen ist dies u. a. auf Tumorrezidive in- oder außerhalb des eigentlichen Behandlungsfelds und weiter distal gelegene Metastasen. Für diese Tumoren ist daher neben den Standardtherapieverfahren Operation und Bestrahlung eine wirksame systemische Behandlung erforderlich. Hierzu bietet sich in erster Linie die antineoplastische Chemotherapie an. Diese hat einen festen Stellenwert im Rahmen der Palliativbehandlung des rezidivierten bzw. metastasierten Krankheitsstadiums sowie in kurativer Intention im Sinne der kombinierten simultanen oder adjuvanten Chemo-Strahlentherapie bei irresektablen bzw. fortgeschrittenen Tumorstadien. Neoadjuvante Therapiestrategien zur Tumorreduktion vor Operation haben sich bislang nicht durchsetzen können. Induktions-Chemotherapieprotokolle vor einer Strahlentherapie wurden bisher bei Patienten mit hohem Fernmetastasierungsrisiko oder als Entscheidungshilfe („Chemoselektion“) bei ausgedehnten Larynxkarzinomen vor einer definitiven Chemo-Radiotherapie bzw. Laryngektomie eingesetzt. Die induzierende 3-fachkombination (Taxane, Cisplatin, 5-Fluorouracil) zeigt bei signifikanter Toxizität hohe Remissionsraten und wird in der Kombination mit einer (Chemo-)Radiotherapie aktuell hinsichtlich Effektivität und Langzeittoxizität mit der simultanen Chemo-Strahlentherapie (Standard) verglichen.

Mit der Vorstellung der Spezifitätserhöhung und Toxizitätsreduktion wurde eine weitere systemische Therapiestrategie entwickelt, die sogenannte „targeted therapy“. Sie wurde in Form von EGFR-spezifischen Antikörpern für die Palliativsituation und die Kombination mit einer Strahlentherapie bei fortgeschrittenen Kopf-Hals-Karzinomen zugelassen. Eine Serie weiterer neuartiger „biologicals“ wie Signalkaskadeninhibitoren, aber auch Gen- oder immuntherapeutische Ansätze werden derzeit in klinischen z. T. groß angelegten Studien evaluiert und könnten zukünftig sinnvoll bei Patienten mit fortgeschrittenen, rezidivierten oder metastasierten Kopf-Hals-Karzinomen eingesetzt werden. Bei der Entwicklung einer nachhaltigen, individualisierten systemischen Tumortherapie stellen entscheidende Evaluationskriterien nicht nur Effektivität und Akuttoxizität sondern auch (langfristige) Lebensqualität und die Identifizierung dezidierter prädiktiver Biomarker dar.

Abstract

Systemic Therapy Strategies for Head-Neck Carcinomas: Current Status

Head and neck cancers, most of which are squamous cell tumours, have an unsatisfactory prognosis despite intensive local treatment. This can be attributed, among other factors, to tumour recurrences inside or outside the treated area, and metastases at more distal locations. These tumours therefore require not only the standard surgical and radiation treatments, but also effective systemic treatment. The main option here is antineoplastic chemotherapy, which is firmly established in the palliative treatment of recurrent or metastatic stages of disease, and is used with curative intent in the form of combined simultaneous or adjuvant chemoradiotherapy in patients with inoperable or advanced tumour stages. Neoadjuvant treatment strategies for tumour reduction before surgery have yet to gain acceptance. Induction chemotherapy protocols before radiotherapy have to date been used in patients at high risk of distant metastases or as an aid for decision-making (“chemoselection”) in those with extensive laryngeal cancers, prior to definitive chemoradiotherapy or laryngectomy. Triple-combination induction therapy (taxanes, cisplatin, 5-fluorouraeil) shows high remission rates with significant toxicity and, in combination with (chemo-)radiotherapy, is currently being compared with simultaneous chemoradiotherapy the current gold standard with regards to efficacy and long-term toxicity.

A further systemic treatment strategy, called ‘targeted therapy’, has been developed to help increase specificity and reduce toxicity. An example of targeted therapy, EGFR-specific antibodies, can be used in palliative settings and, in combination with radiotherapy, to treat advanced head and neck cancers. A series of other novel biologicals such as signal cascade inhibitors, genetic agents, or immunotherapies, are currently being evaluated in large-scale clinical studies, and could prove useful in patients with advanced, recurring or metastatic head and neck cancers. When developing a lasting, individualised systemic tumour therapy, the critical evaluation criteria are not only efficacy and acute toxicity but also (Iong-term) quality-of-life and the identification of dedicated predictive biomarkers.

Schlüsselwörter:

Kopf-Hals-Karzinom - Plattenepithelkarzinom - Chemotherapie - Immuntherapie - Targeted Therapy - Antikörper

Key words

head-neck carcinoma - squamous-cell carcinoma of the head and neck - medical therapy - chemotherapy - antibody - targeted therapy - biological
 

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