Subscribe to RSS
DOI: 10.1055/s-2005-921107
Palliative Chemotherapie von Kopf-Hals-Tumoren: Aktueller Stand und neue Entwicklungen
Palliative Chemotherapy of Head and Neck Cancer: Present Status and Future DevelopmentPublication History
Eingegangen: 26. Juni 2005
Angenommen: 19. Oktober 2005
Publication Date:
17 March 2006 (online)
![](https://www.thieme-connect.de/media/lro/200603/lookinside/thumbnails/10.1055-s-2005-921107-1.jpg)
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.
Schlüsselwörter
Kopf-Hals-Tumore - Chemotherapie - Taxane - Cisplatin - molekulare Therapie
Key words
Head and neck neoplasms - chemotherapy - taxanes - cisplatin - molecular therapy
Literatur
- 1 Lang S, Wollenberg B, Dellian M, Steuer-Vogt M K, Schwenzer K, Sautier W, Chucholowski M, Eckel R, Faas I, Wilmes E, Ehrenfeld M, Arnold W, Kastenbauer E, Holzel D. Klinische und epidemiologische Daten zu Malignomen des Kopf-Hals-Bereichs. Larngo-Rhino-Otol. 2002; 81 499-508
- 2 Vokes E E, Weichselbaum R R, Lippman S M, Hong W K. Head and neck cancer. N Engl J Med. 1993; 328 184-194
- 3 Kath R. Chemotherapie bei Kopf-Hals-Karzinomen. Onkologe. 2001; 7 557-562
- 4 Schrijvers D, Vermorken J B. Role of taxoids in head and neck cancer. Oncologist. 2000; 5 199-208
- 5 Catimel G, Vermorken J B, Clavel M, de Mulder P, Judson I, Sessa C, Piccart M, Bruntsch U, Verweij J, Wanders J, Franklin H, Kaye S B. A phase II study of Gemcitabine (LY 188011) in patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. Ann Oncol. 1994; 5 543-547
- 6 Samlowski W E, Gundacker H, Kuebler J P, Giguere J K, Mills G M, Schuller D E, Ensley J F. Evaluation of gemcitabine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Southwest Oncology Group phase II study. Invest New Drugs. 2001; 19 311-315
- 7 Testolin A, Recher G, Cristoferi V, Gasparini G. Vinorelbine in pre-treated advanced head & neck squamous cell carcinoma. A phase II study. Invest New Drugs. 1994; 12 231-234
- 8 Degardin M, Oliveira J, Geoffrois L, Rolland F, Armand J P, Bastit P, Chauvergne J, Fargeot P, van Glabbeke M, Lentz M A, Tresca P, Boudillet J, Fumoleau P, Cappelaere P. An EORTC-ECSG phase II study of vinorelbine in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 1998; 9 1103-1107
- 9 Saxman S, Mann B, Canfield V, Loehrer P, Vokes E. A phase II trial of vinorelbine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Am J Clin Oncol. 1998; 21 398-400
- 10 Jacobs C, Lyman G, Velez-Garcia E, Sridhar K S, Knight W, Hochster H, Goodnough L T, Mortimer J E, Einhorn L H, Schacter L, Cherng N, Dalton T, Burroughs J, Rozencweig M. A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol. 1992; 10 257-263
- 11 Forastiere A A, Metch B, Schuller D E, Ensley J F, Hutchins L F, Triozzi P, Kish J A, McClure S, VonFeldt E, Williamson S K, Von Hoff D D. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. J Clin Oncol. 1992; 10 1245-1251
-
12 Kurzgefasste Interdisziplinäre Leitlinien .. Deutsche Krebsgesellschaft e. V München; W. Zuckschwerdt Verlag 2004
- 13 Clavel M, Vermorken J B, Cognetti F, Cappelaere P, de Mulder P H, Schornagel J H, Tueni E A, Verweij J, Wildiers J, Clerico M, Dalesio O, Kirkpatrick A, Snow G B. Randomized comparison of cisplatin, methotrexate, bleomycin and vincristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in recurrent or metastatic squamous cell carcinoma of the head and neck. A phase III study of the EORTC Head and Neck Cancer Cooperative Group. Ann Oncol. 1994; 5 521-526
- 14 Pivot X, Chamorey E, Guardiola E, Magne N, Thyss A, Otto J, Giroux B, Mouri Z, Schneider M, Milano G. Phase I and pharmacokinetic study of the association of capecitabine-cisplatin in head and neck cancer patients. Ann Oncol. 2003; 14 1578-1586
- 15 Hitt R, Jimeno A, Rodriguez-Pinilla M, Rodriguez-Peralto J L, Millan J M, Lopez-Martin A, Brandariz A, Pena C, Cortes-Funes H. Phase II trial of cisplatin and capecitabine in patients with squamous cell carcinoma of the head and neck, and correlative study of angiogenic factors. Br J Cancer. 2004; 91 2005-2011
- 16 Adamo V, Ferraro G, Pergolizzi S, Sergi C, Laudani A, Settineri N, Alafaci E, Scimone A, Spano F, Spitaleri G. Paclitaxel and cisplatin in patients with recurrent and metastatic head and neck squamous cell carcinoma. Oral Oncol. 2004; 40 525-531
- 17 Moosmann P, Egli F, Stahel R A, Jost L. Weekly paclitaxel and carboplatin combination chemotherapy in patients with advanced squamous cell carcinoma of the head and neck. Onkologie. 2003; 26 568-572
- 18 Fountzilas G, Athanassiades A, Kalogera-Fountzila A, Samantas E, Bacoyiannis C, Briassoulis E, Pavlidis N, Kosmidis P, Skarlos D. Paclitaxel in combination with carboplatin or gemcitabine for the treatment of advanced head and neck cancer. Semin Oncol. 1997; 24 S19
- 19 Murphy B, Li Y, Cella D. Phase III study comparing cisplatin and 5-fluorouracil versus cisplatin and paclitaxel in metastatic/recurrent head and neck cancer. Proc Am Soc Clin Oncol. 2001; 20 224 (abstract)
- 20 Glisson B S, Murphy B A, Frenette G, Khuri F R, Forastiere A A. Phase II Trial of docetaxel and cisplatin combination chemotherapy in patients with squamous cell carcinoma of the head and neck. J Clin Oncol. 2002; 20 1593-1599
- 21 Hitt R, Castellano D, Hidalgo M, Garcia-Carbonero R, Pena M, Brandariz A, Millan J M, Alvarez Vincent J J, Cortes-Funes H. Phase II trial of cisplatin and gemcitabine in advanced squamous-cell carcinoma of the head and neck. Ann Oncol. 1998; 9 1347-1349
- 22 Gebbia V, Mantovani G, Agostara B, Contu A, Farris A, Colucci G, Cognetti F, Restivo G, Speciale R, Ferrero B, Testa A, Curreli L, Cardinale A, Bajetta E, Gebbia N. Treatment of recurrent and/or metastatic squamous cell head and neck carcinoma with a combination of vinorelbine, cisplatin, and 5-fluorouracil: a multicenter phase II trial. Ann Oncol. 1995; 6 987-991
- 23 Gebbia V, Testa A, Di Gregorio C, Ingria F, Valenza R, Cannata G, Moschella F, Restivo G, Gebbia N. Vinorelbine plus cisplatin in recurrent or previously untreated unresectable squamous cell carcinoma of the head and neck. Am J Clin Oncol. 1995; 18 293-296
- 24 Gebbia V, Mantovani G, Farris A, Agostara B, Desogus A, Curreli L, Moschella F, Di Gregorio C, Bajetta E, Gebbia N. Vinorelbine, cisplatin, and 5-fluorouracil as initial treatment for previously untreated, unresectable squamous cell carcinoma of the head and neck: results of a phase II multicenter study. Cancer. 1997; 79 1394-1400
- 25 Genet D, Cupissol D, Calais G, Bontemps P, Bourgeois H, Dutin J P, Philippi M H, Bendahmane B, Mallard-Carre M, Tubiana-Mathieu N. Docetaxel plus 5-fluorouracil in locally recurrent and/or metastatic squamous cell carcinoma of the head and neck: a phase II multicenter study. Am J Clin Oncol. 2004; 27 472-476
- 26 Airoldi M, Cattel L, Marchionatti S, Recalenda V, Pedani F, Tagini V, Bumma C, Beatrice F, Succo G, Maria G A. Docetaxel and vinorelbine in recurrent head and neck cancer: pharmacokinetic and clinical results. Am J Clin Oncol. 2003; 26 378-381
- 27 Cupissol D, Calais G, Tourani J M, Kohser F, Borel C, Eymard J C, Dubin F, Ecstein-Fraisse E, Tubiana-Mathieu N. Phase II Study of Docetaxel plus Gemcitabine in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck. Proc Am Soc Clin Oncol. 2003; 22 508 (abstract)
- 28 Modjtahedi H. Molecular therapy of head and neck cancer. Cancer Metastasis Rev. 2005; 24 129-146
- 29 Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, Knecht R, Amellal N, Bessa E H, Baselga J, Vermorken J B. Cetuximab monotherapy is active in patients (pts) with platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN): Results of a phase II study. J Clin Oncol. 2004; 22 5502 (abstract)
- 30 Herbst R S, Arquette M, Shin D M, Dicke K, Vokes E E, Azarnia N, Hong W K, Kies M S. Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol. 2005; 23 5578-5587
- 31 Baselga J, Trigo J M, Bourhis J, Tortochaux J, Cortes-Funes H, Hitt R, Gascon P, Amellal N, Harstrick A, Eckardt A. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2005; 23 5568-5577
- 32 Burtness B, Li Y, Flood W, Mattar B I, Forastiere A A. Phase III trial comparing cisplatin (C) + placebo (P) to C + anti-epidermal growth factor antibody (EGF-R) C225 in patients (pts) with metastatic/recurrent head & neck cancer (HNC). Proc Am Soc Clin Oncol. 2002; 21 226 (abstract)
- 33 Burtness B. The role of cetuximab in the treatment of squamous cell cancer of the head and neck. Expert Opin Biol Ther. 2005; 5 1085-1093
- 34 Cohen E E, Rosen F, Stadler W M, Recant W, Stenson K, Huo D, Vokes E E. Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2003; 21 1980-1987
- 35 Wheeler R H, Jones D, Sharma P, Davis R K, Spilker H, Boucher K, Leachman S, Grossman K, Salzman K, Akerley W. Clinical and molecular phase II study of gefitinib in patients (pts) with recurrent squamous cell cancer of the head and neck (H&N Ca). J Clin Oncol. 2005; 23 507s (abstract)
- 36 Belón J, Irigoyen A, Rodríguez I, Escobar Y, Alonso J, Pastor P, Valdivia J, Concha A, Nuevo J, Bovio H. Preliminary results of a Phase II study to evaluate gefitinib combined with docetaxel and cisplatin in patients with recurrent and/or metastatic squamous-cell carcinoma of the head and neck. J Clin Oncol. 2005; 23 515s (abstract)
- 37 Schoffski P, Catimel G, Planting A S, Droz J P, Verweij J, Schrijvers D, Gras L, Schrijvers A, Wanders J, Hanauske A R. Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. Ann Oncol. 1999; 10 119-122
- 38 Specht L, Larsen S K, Hansen H S. Phase II study of docetaxel and cisplatin in patients with recurrent or disseminated squamous-cell carcinoma of the head and neck. Ann Oncol. 2000; 11 845-849
- 39 Hitt R, Jimeno A, Millan J M, Castellano D, Cortes-Funes H. Phase II trial of dose-dense paclitaxel, cisplatin, 5-fluorouracil, and leucovorin with filgrastim support in patients with squamous cell carcinoma of the head and neck. Cancer. 2004; 101 768-775
- 40 Schena M, Barone C, Birocco N, Dongiovanni D, Numico G, Colantonio I, Bertetto O. Weekly cisplatin paclitaxel and continuous infusion fluorouracil in patients with recurrent and/or metastatic head and neck squamous cell carcinoma: a phase II study. Cancer Chemother Pharmacol. 2005; 55 271-276
- 41 Iop A, Cartei G, Isaia A. Vinorelbine, bleomycin and methotrexate as a salvage therapy for patients with head and neck squamous carcinoma in relapse after cisplatin/fluorouracil. Ann Oncol. 1998; 9 225-227
- 42 Fountzilas G, Stathopoulos G, Nicolaides C, Kalogera-Fountzila A, Kalofonos H, Nikolaou A, Bacoyiannis C, Samantas E, Papadimitriou C, Kosmidis P, Daniilidis J, Pavlidis N. Paclitaxel and gemcitabine in advanced non-nasopharyngeal head and neck cancer: a phase II study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol. 1999; 10 475-478
- 43 Airoldi M, Cattel L, Cortesina G, Giordano C, Passera R, Pedani F, Novello S, Bumma C, Gabriele P. Gemcitabine and vinorelbine in recurrent head and neck cancer: pharmacokinetic and clinical results. Anticancer Res. 2003; 23 2845-2852
Priv.-Doz. Dr. Burkhard Hennemann
Abteilung für Hämatologie und Onkologie · Universitätsklinikum Regensburg (Leiter Prof. Dr. Reinhard Andreesen)
Franz-Josef-Strauß-Allee 11 · 93042 Regensburg ·
Email: burkhard.hennemann@klinik.uni-regensburg.de