Palliative Chemotherapie von Kopf-Hals-Tumoren: Aktueller Stand und neue Entwicklungen

Zusammenfassung

Hintergrund: Die palliative Chemotherapie von Patienten mit Kopf-Hals-Tumoren wird bei Auftreten von Metastasen oder bei lokoregionärem Rezidiv ohne weitere chirurgische oder strahlentherapeutische Optionen eingesetzt. Neben 5-Fluorouracil (5-FU) plus Cisplatin oder Carboplatin kommen neue Substanzen wie Taxane, Gemcitabin und Vinorelbin und molekulare Therapieansätze mit monoklonalen Antikörpern und Signaltransduktionshemmern zum Einsatz.

Methode: Die vorliegende Übersicht analysiert und wertet die publizierte Literatur der letzten 15 Jahre einschließlich ausgewählter online verfügbarer Kongressbeiträge im Hinblick auf Ansprechen, Überlebenszeit und Nebenwirkungen.

Ergebnisse: Die Kombination von Cisplatin oder Carboplatin mit 5-FU kann unverändert als Standardtherapie gelten und erzielt Remissionsraten von 20 - 30 %. Durch Hinzufügen von Taxanen lässt sich das Ansprechen möglicherweise steigern jedoch um den Preis einer ausgesprochen hohen Toxizität. Kombinationen von Cisplatin mit Taxotere oder Paclitaxel anstelle von 5-FU scheinen äquipotent und verträglicher zu sein. Große Phase-III-Studien, die eine Verlängerung des Gesamtüberlebens durch die Kombinationschemotherapie im Vergleich zur Monotherapie belegen, fehlen, so dass bei Patienten mit reduziertem Allgemeinzustand der Versuch einer Monochemotherapie gerechtfertigt ist. Eine Rezidivtherapie nach Versagen einer platinhaltigen Chemotherapie sollte nur ausgewählten Patienten angeboten werden. In dieser Indikation sind platinfreie Kombinationen von Taxanen, Gemcitabin und Vinorelbin Erfolg versprechend. Erste Studien berichten über eine Ansprechrate von ca. 10 - 20 % nach Therapie mit monoklonalen Antikörpern oder niedermolekularen Tyrosinkinase-Inhibitoren.

Schlussfolgerung: Durch die Hinzunahme neuer Substanzen lassen sich möglicherweise das Ansprechen und die Verträglichkeit der Chemotherapie verbessern. Große Phase-III-Studien sind jedoch notwendig, um die Verlängerung der Lebenszeit zu belegen. Molekulare Therapieansätze bereichern das therapeutische Arsenal, und ermöglichen vielleicht in Zukunft ein Überwinden der Chemotherapieresistenz.

Abstract

Background: Patients with head and neck tumors are treated with palliative chemotherapy in case of the detection of distant metastases or local recurrence without the option of surgical therapy or radiation. Alongside 5-fluorouracil (5-FU) in combination with cisplatin or carboplatin, taxanes, gemcitabine and vinorelbine as well as monoclonal antibodies or small molecule tyrosine kinase inhibitors have been used.

Methods: This review analyses the published literature of the past 15 years, including selected abstracts with view to response rate, overall survival and adverse effects.

Results: 5-FU plus cisplatin or carboplatin can still be considered as standard treatment, achieving response rates of 20 - 30 %. The addition of taxanes increases the objective response rate but adds remarkable toxicity to the treatment protocol. Phase III studies demonstrate higher response rates but fail to demonstrate a significant increase of the overall survival after polychemotherapy as compared to monotherapy protocols. Thus, patients with a reduced performance can be treated with monotherapy. In case of disease progression after cisplatin-containing chemotherapy further treatment should only be offered to selected patients. For this situation, platin-free chemotherapy protocols containing taxanes, gemcitabine or vinorelbine seem promising. Recent studies with monoclonal antibodies or small molecule tyrosine kinase inhibitors report on a response rate of 10 - 20 %.

Conclusion: The use of new drugs increases the response rate and amends the side effects of the chemotherapy. However, phase III studies documenting an improved overall survival are lacking. Targeted therapies broaden the therapeutic armament, and possibly, EGFR inhibition will help to overcome chemotherapy resistance in the future.

Kopf-Hals-Tumore - Chemotherapie - Taxane - Cisplatin - molekulare Therapie

Head and neck neoplasms - chemotherapy - taxanes - cisplatin - molecular therapy

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