Abstract
Most patients with recurrent or metastatic head and neck squamous cell cancers qualify for palliative treatment. The management of these patients includes supportive care only, mono- or multiagent chemotherapy, and more recently targeted therapies. While platinum-based combinations are superior to single-agent therapies in terms of response rate, they are more toxic and so far have not shown to lead to meaningful survival benefit. Attempts to improve on this by using other or additional cytotoxic drugs were unsuccessful in the last 30 years. It was therefore an urgent need to investigate the efficacy of novel anticancer therapies that specifically target the tumor cells in such patients. A recent randomized trial showed that adding cetuximab, an EGFR-directed monoclonal antibody, to a standard platinum-based chemotherapy regimen led to an important survival benefit. Despite the still dismal prognosis, the outcome of this latter trial has changed practice in this category of head and neck cancer patients. The next challenge will be to sort out how to incorporate the numerous targeted agents that are currently studied into the existing treatment strategies, also in consideration of an optimization of their therapeutic index. Human papillomavirus status with immunohistochemical p16 expression as its surrogate marker represents promising prognostic and possibly predictive biomarkers that need to be prospectively validated in future randomized trials.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Licitra L, Locati LD, Bossi P. Optimizing approaches to head and neck cancer. Metastatic head and neck cancer: new options. Ann Oncol. 2008;19:vii200–3.
Vermorken JB. Medical treatment in head and neck cancer. Ann Oncol. 2005;16:ii258–64.
Colevas AD. Chemotherapy options for patients with metastatic or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2006;24:2644–52.
Al-Sarraf M. Head and neck cancer: chemotherapy concepts. Semin Oncol. 1988;15:70–85.
Amer MH, Al-Sarraf M, Vaitkevicius VK. Factors that affect response to chemotherapy and survival of patients with advanced head and neck cancer. Cancer. 1979;42:2202–6.
Forastiere AA, Metch B, Schuller DE, et al. 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;10:1245–51.
Jacobs C, Lyman G, Velez-GarcÃa E, et al. 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;10:257–63.
Stell PM, McCormick MS. The design of phase III palliative chemotherapy trials in head and neck cancer. Clin Otolaryngol Allied Sci. 1986;11:21–9.
Argiris A, Li Y, Forastiere A. Prognostic factors and long/term survivorship in patients with recurrent or metastatic carcinoma of the head and neck. An analysis of two Eastern Cooperative Oncology Group randomized trials. Cancer. 2004;101:2222–9.
León X, Hitt R, Constenla M, et al. A retrospective analysis of the outcome of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck refractory to a platinum-based chemotherapy. Clin Oncol. 2005;17:418–24.
Pivot X, Wadler S, Kelly C, et al. Result of two randomized trials comparing nolatrexed (Thymitaq) versus methotrexate in patients with recurrent head and neck cancer. Ann Oncol. 2001;12:1595–9.
Stewart JS, Cohen EE, Licitra L, et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2009;27:1864–71.
Machiels JP, Subramanian S, Ruzsa A, et al. Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: an open-label, randomised phase 3 trial. Lancet Oncol. 2011;12:333–43.
Numico G, Merlano M. Second-line treatment with docetaxel after failure of a platinum-based chemotherapy in squamous-cell head and neck cancer. Ann Oncol. 2002;13:331–3.
Zenda S, Onozawa Y, Boku N, Iida Y, Ebihara M, Onitsuka T. Single-agent docetaxel in patients with platinum-refractory metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). Jpn J Clin Oncol. 2007;37:477–81.
Specenier P, Rasschaert M, Vroman P, et al. Weekly docetaxel in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Am J Clin Oncol. 2011;34:472–7.
Argiris A, Ghebremichael M, Gilbert J, et al. Phase III randomized, placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic head and neck cancer: an eastern cooperative oncology group trial. J Clin Oncol. 2013;31:1405–14.
Urba SG, Forastiere AA. Systemic therapy of head and neck cancer: most effective agents, areas of promise. Oncology (Williston Park). 1989;4:79–88.
Kish JA, Ensley JF, Jacobs J, Weaver A, Cummings G, Al-Sarraf M. A randomized trial of cisplatin (CACP) and 5-fluorouracil (5-FU) infusion and CACP + 5-FU bolus for recurrent and advanced squamous cell carcinoma of the head and neck. Cancer. 1985;56:2740–4.
Amrein PC, Weitzman SA. Treatment of squamous cell carcinoma of the head and neck with cisplatin and 5-fluorouracil. J Clin Oncol. 1985;3:1632–9.
Tannock IF. Chemotherapy for head and neck cancer. J Otolaryngol. 1984;13:99–104.
Al-Sarraf M. Chemotherapy strategies in squamous cell carcinoma of the head and neck. Crit Rev Oncol Hematol. 1984;1:323–55.
Carter SK, Slavik M. Current investigational drugs of interest in the chemotherapy program of the National Cancer Institute. Natl Cancer Inst Monogr. 1977;45:101–21.
Clavel M, Vermorken JB, Cognetti F, et al. 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;5:521–6.
Hong WK, Schaefer S, Issell B, et al. A prospective randomized trial of methotrexate versus cisplatin in the treatment of recurrent squamous cell carcinoma of the head and neck. Cancer. 1983;52:206–10.
Eisenberger M, Hornedo J, Silva H, et al. Carboplatin (NSC-241-240): an active platinum analog for the treatment of squamous-cell carcinoma of the head and neck. J Clin Oncol. 1986;4:1506–9.
Wittes RE. Chemotherapy of head and neck cancer. Otolaryngol Clin North Am. 1980;13:515–20.
Glick JH, Zehngebot LM, Taylor SG. Chemotherapy for squamous cell carcinoma of the head and neck: a progress report. Am J Otolaryngol. 1980;1:306–23.
Airoldi M, Cortesina G, Giordano C, et al. Ifosfamide in the treatment of head and neck cancer. Oncology. 2003;65(Suppl2):37–43.
Schrijvers D, Vermorken JB. Taxanes in head and neck cancer. Future Oncol. 2005;1:829–39.
Grau JJ, Caballero M, Verger E, Monzo M, Blanch JL. Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients. Acta Otolaryngol. 2009;129:1294–9.
Pivot X, Raymond E, Laguerre B, et al. Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck. Br J Cancer. 2001;85:649–55.
Testolin A, Recher G, Cristoferi V, et al. Vinorelbine in pre-treated advanced head and neck squamous cell carcinoma: a phase II study. Invest New Drugs. 1994;12:213–34.
Degardin M, Oliveira J, Geoffrois L, et al. 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;9:1103–7.
Martinez-Trufero J, Isla D, Adansa JC, et al. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment. Br J Cancer. 2010;102:1687–91.
Murphy BA. Topoisomerases in the treatment of metastatic or recurrent squamous carcinoma of the head and neck. Expert Opin Pharmacother. 2005;6:85–92.
Kuebler JP, Benedetti J, Schuller DE, et al. Phase II study of edatrexate in advanced head and neck cancer. A Southwest Oncology Group study. Invest New Drugs. 1994;12:341–4.
Schornagel JH, Verweij J, de Mulder PH, et al. Randomized phase III trial of edatrexate versus methotrexate in patients with metastatic and/or recurrent squamous cell carcinoma of the head and neck: a European Organization for Research and Treatment of Cancer Head and Neck Cancer Cooperative Group study. J Clin Oncol. 1995;13:1649–55.
Park S, Lee S, Park J, Cho E, Shin D, Lee J. Phase II study of oral S-1 in pretreated patients with recurrent or metastatic head and neck cancer. J Clin Oncol. 2008;26:692s. Abstract 17007.
Hitt R, Amador ML, Quintela-Fandino M, et al. Weekly docetaxel in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Cancer. 2006;106:106–11.
Colevas AD, Amrein PC, Gomolin H, et al. A phase II study of combined oral uracil and ftorafur with leucovorin for patients with squamous cell carcinoma of the head and neck. Cancer. 2001;92:326–31.
Grose WE, Lehane DE, Dixon DO, Fletcher WS, Stuckey WJ. Comparison of methotrexate and cisplatin for patients with advanced squamous cell carcinoma of the head and neck region: a Southwest Oncology Group study. Cancer Treat Rep. 1985;69:577–81.
Vermorken JB, Catimel G, de Mulder P, et al. Randomized phase II trial of weekly methotrexate versus two schedules of three-weekly paclitaxel in patients with metastatic or recurrent squamous cell carcinoma of the head and neck. Proc Am Soc Clin Oncol. 1999;18:395a. Abstract 1527.
Guardiola E, Peyrade F, Chaigneau L, et al. Results of a randomised phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer. Eur J Cancer. 2004;40:2071–6.
Morton RP, Rugman F, Dorman EB, et al. Cisplatinum and bleomycin for advanced or recurrent squamous cell carcinoma of the head and neck: a randomised factorial phase III controlled trial. Cancer Chemother Pharmacol. 1985;15:283–9.
De Andres L, Brunet J, Lopez-Pousa A, et al. Randomized trial of neoadjuvant cisplatin and fluorouracil versus carboplatin and fluorouracil in patients with stage IV-M0 head and neck cancer. J Clin Oncol. 1995;13:1493–500.
Eisenberger M, Krasnow S, Ellenberg S, et al. A comparison of carboplatin plus methotrexate versus methotrexate alone in patients with recurrent and metastatic head and neck cancer. J Clin Oncol. 1989;7:1341–5.
Clavel M, Cognetti F, Dodion P, et al. Combination chemotherapy with methotrexate, bleomycin, and vincristine with or without cisplatin in advanced squamous cell carcinoma of the head and neck. Cancer. 1987;60:1173–7.
Urba S, van Herpen CM, Sahoo TP, et al. Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer: final results of a randomized, double-blind, placebo-controlled, phase 3 study. Cancer. 2012;118:4694–705.
Schantz SP, Harrison LB, Forastiere AA. Tumors of the nasal cavity and paranasal sinuses, nasopharynx, oral cavity, and oropharynx. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles & practice of oncology. 6th ed. Philadelphia: Lippincott-Raven; 2001. p. 797–860.
Shin DM, Glisson BS, Khuri FR, et al. Phase II trial of paclitaxel, ifosfamide, and cisplatin in patients with recurrent head and neck squamous cell carcinoma. J Clin Oncol. 1998;16:1325–30.
Shin DM, Khuri FR, Glisson BS, et al. Phase II study of paclitaxel, ifosfamide, and carboplatin in patients with recurrent or metastatic head and neck squamous cell carcinoma. Cancer. 2001;91:1316–23.
Samlowski WE, Moon J, Kuebler JP, et al. Evaluation of the combination of docetaxel/carboplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN): a Southwest Oncology Group phase II study. Cancer Invest. 2007;25:182–8.
Gibson MK, Li Y, Murphy B, et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an Intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2005;23:3562–7.
Janinis J, Papadakou M, Xidakis E, et al. Combination chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in previously treated patients with advanced/recurrent head and neck cancer: a phase II feasibility study. Am J Clin Oncol. 2000;23:128–31.
Benasso M, Ponzanelli A, Merlano M, et al. Paclitaxel, cisplatin and 5-fluorouracil in recurrent squamous cell carcinoma of the head and neck: a phase II trial from an Italian cooperative group. Acta Oncol. 2006;45:168–74.
Specenier P, Vermorken JB. Targeted therapies in head and neck cancer. Targeted Oncol. 2007;2:73–8.
Ugurluer G, Ozsahin M. Early investigational drugs that target epidermal growth factor receptors for the treatment of head and neck cancer. Expert Opin Investig Drugs. 2014;23:1637–54.
Schmitz S, Ang KK, Vermorken J, et al. Targeted therapies for squamous cell carcinoma of the head and neck: current knowledge and future directions. Cancer Treat Rev. 2014;40:390–404.
Zandberg DP, Strome SE. The role of the PD-L1:PD-1 pathway in squamous cell carcinoma of the head and neck. Oral Oncol. 2014;50:627–32.
Xia W, Lau YK, Zhang HZ, et al. Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin Cancer Res. 1999;5:4164–74.
Ang KK, Berkey BA, Tu X, et al. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002;62:7350–6.
Chung CH, Ely K, McGavran L, et al. Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol. 2006;24:4170–6.
Eriksen JG, Steiniche T, Askaa J, et al. The prognostic value of epidermal growth factor receptor is related to tumor differentiation and the overall treatment time of radiotherapy in squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys. 2004;58:561–6.
Santini J, Formento JL, Francoual M, et al. Characterization, quantification, and potential clinical value of the epidermal growth factor receptor in head and neck squamous cell carcinomas. Head Neck. 1991;13:132–9.
Licitra L, Störkel S, Kerr KM, et al. Predictive value of epidermal growth factor receptor expression for first-line chemotherapy plus cetuximab in patients with head and neck and colorectal cancer: analysis of data from the EXTREME and CRYSTAL studies. Eur J Cancer. 2013;49:1161–8.
Licitra L, Mesia R, Rivera F, et al. Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study. Ann Oncol. 2011;22:1078–87.
Scaltriti M, Baselga J. The epidermal growth receptor pathway: a model for targeted therapy. Clin Cancer Res. 2006;12:5268–72.
Kimura H, Sakai K, Arao T, Shimoyama T, Tamura T, Nishio K. Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci. 2007;98:1275–80.
Bleeker WK, Lammerts van Bueren JJ, van Ojik HH, et al. Dual mode of action of a human anti-epidermal growth factor receptor monoclonal antibody for cancer therapy. J Immunol. 2004;173:4699–707.
Schneider-Merck T, Lammerts van Bueren JJ, Berger S, et al. Human IgG2 antibodies against epidermal growth factor receptor effectively trigger antibody-dependent cellular cytotoxicity but, in contrast to IgG1, only by cells of myeloid lineage. J Immunol. 2010;184:512–20.
Rapidis AD, Vermorken JB, Bourhis J. Targeted therapies in head and neck cancer: past, present and future. Rev Recent Clin Trials. 2008;3:156–66.
Huang S, Armstrong EA, Benavente S, Chinnaiyan P, Harari PM. Dual-agent molecular targeting of the epidermal growth factor receptor (EGFR): combining anti-EGFR antibody with tyrosine kinase inhibitor. Cancer Res. 2004;64:5355–62.
Matar P, Rojo F, Cassia R, et al. Combined epidermal growth factor receptor targeting with the tyrosine kinase inhibitor gefitinib (ZD1839) and the monoclonal antibody cetuximab (IMC-C225): superiority over single-agent receptor targeting. Clin Cancer Res. 2004;10:6487–501.
Baselga J, Trigo JM, Bourhis J, et al. 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;23:5568–77.
Herbst RS, Arquette M, Shin DM, et al. 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;23:5578–87.
Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007;25:2171–7.
Bourhis J, Rivera F, Mesia R, et al. Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2006;24:2866–72.
Hitt R, Irigoyen A, Cortes-Funes H, et al. Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. Ann Oncol. 2012;23:1016–22.
Buentzel J, de Vries A, Micke O. Experience with cetuximab plus paclitaxel/carboplatinum in primary platinum-resistant recurrent head and neck cancer. J Clin Oncol. 2007;25:318s. Abstract 6077.
Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA, Eastern Cooperative Oncology Group. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005;23:8646–54.
Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–27.
Vermorken JB, Remenar E, Hitt R, et al. Platinum-based chemotherapy (CT) plus cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck cancer (R/M-SCCHN): 5-year follow-up data for the extreme trial. J Clin Oncol. 2014;32:5s. Abstract 6021.
Petrelli NJ, Winer EP, Brahmer J, et al. Clinical cancer advances 2009 major research advances in cancer treatment, prevention, and screening—a report from the American Society of Clinical Oncology. J Clin Oncol. 2009;27:6052–69.
Guigay J, Fayette J, Dillies AF, et al. Cetuximab, docetaxel, and cisplatin (TPEx) as first-line treatment in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): final results of phase II trial GORTEC 2008-03. J Clin Oncol. 2012;30:15s. Abstract 5505.
Vermorken JB, Licitra L, Stöhlmacher-Williams J, et al. Phase II study of pemetrexed in combination with cisplatin and cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck. Eur J Cancer. 2013;49:2877–83.
Carteni G, Fiorentino R, Vecchione L, Chiurazzi B, Battista C. Panitumumab a novel drug in cancer treatment. Ann Oncol. 2007;18:vi16–21.
Rishchin D, Spigel D, Adkins D, et al. PRISM: primary efficacy results of a phase 2 trial with panitumumab monotherapy as second-line treatment with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). In: Multidisciplinary head and neck symposium; 2011. Abstract 169.
Wirth LJ, Dakhil SR, Kornek G, et al. PARTNER: a randomized phase II study of docetaxel/cisplatin (doc/cis) chemotherapy with or without panitumumab (pmab) as first-line treatment (tx) for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). J Clin Oncol. 2013;31. Abstract 6029.
Vermorken JB, Stöhlmacher-Williams J, Davidenko I, et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 2013;14:697–710.
Bier H, Hoffman T, Hauser U, et al. Clinical trial with escalating doses of the antiepidermal growth factor receptor humanized monoclonal antibody EMD72000 in patients with advanced squamous cell carcinoma of the larynx and hypopharynx. Cancer Chemother Pharmacol. 2001;47:519–24.
Arteaga ME, Ledón N, Casacó A, et al. Systemic and skin toxicity in Cercopithecus aethiops sabaeus monkeys treated during 26 weeks with a high intravenous dose of the anti-epidermal growth factor receptor monoclonal antibody nimotuzumab. Cancer Biol Ther. 2007;6:1390–5.
Ramakrishnan MS, Eswaraiah A, Crombet T, et al. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. mAbs. 2009;1:41–8.
Soulieres D, Senzer NN, Vokes EE, Hidalgo M, Agarwala SS, Siu LL. Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. J Clin Oncol. 2004;22:77–85.
Cohen EE, Rosen F, Stadler WM, et al. Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2003;21:1980–7.
Cohen EE, Kane MA, List MA, et al. Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Clin Cancer Res. 2005;11:8418–24.
Kirby AM, A’Hern RP, D’Ambrosio C, et al. Gefitinib (ZD1839, Iressa) as palliative treatment in recurrent or metastatic head and neck cancer. Br J Cancer. 2006;94:631–6.
De Souza JA, Davis DW, Zhang Y, et al. A phase II study of lapatinib in recurrent/metastatic squamous cell carcinoma of the head and neck. Clin Cancer Res. 2012;18:2336–43.
Cohen EE, Halpern AB, Kasza K, et al. Factors associated with clinical benefit from epidermal growth factor receptor inhibitors in recurrent and metastatic squamous cell carcinoma of the head and neck. Oral Oncol. 2009;45:155–60.
Seiwert TY, Fayette J, Cupissol D, et al. A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck. Ann Oncol. 2014;25:1813–20.
Abdul Razak AR, Soulières D, Laurie SA, et al. A phase II trial of dacomitinib, an oral pan-human EGF receptor (HER) inhibitor, as first-line treatment in recurrent and/or metastatic squamous-cell carcinoma of the head and neck. Ann Oncol. 2013;24:761–9.
Machiels JP, Haddad RI, Fayette J, et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 2015;16:583–94.
Siu LL, Soulieres D, Chen EX, et al. Phase I/II trial of erlotinib and cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Princess Margaret Hospital phase II consortium and National Cancer Institute of Canada Clinical Trials Group study. J Clin Oncol. 2007;25:2178–83.
Belon J, Irigoyen A, Rodriguez I, et al. 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 5563.
Kim ES, Kies MS, Glisson BS, et al. Final results of a phase II study of erlotinib, docetaxel and cisplatin in patients with recurrent/metastatic head and neck cancer. J Clin Oncol. 2007;25:302s. Abstract 5521.
Weiss J, Hayes DN, Algazy K, et al. Combination lapatinib and capecitabine in advanced, incurable squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol. 2013;31. Abstract 6094.
Boeckx C, Baay M, Wouters A, et al. Anti-epidermal growth factor receptor therapy in head and neck squamous cell carcinoma: focus on potential molecular mechanisms of drug resistance. Oncologist. 2013;18:850–64.
Fayette J, Wirth L, Oprean C, Hitt R, Udrea A, Jimeno A, et al. Randomized phase II study of MEHD7945A (MEHD) vs cetuximab (Cet) in >= 2nd-line recurrent/metastatic squamous cell Carcinoma of the head & neck (RMSCCHN) progressive on/after platinum-based chemotherapy (PtCT). Ann Oncol. 2014;25:iv340–56. Abstract 986O.
Vermorken JB. Molecular targeted drugs for head and neck cancer. Ann Oncol. 2013;24:ix21. Abstract SY4–1.
Kyzas PA, Stefanou D, Batistatou A, Agnantis NJ. Prognostic significance of VEGF immunohistochemical expression and tumor angiogenesis in head and neck squamous cell carcinoma. J Cancer Res Clin Oncol. 2005;131:624–30.
Kyzas PA, Cunha IW, Ioannidis JP. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res. 2005;11:1434–40.
Seiwert TY, Haraf DJ, Cohen EEW, et al. Phase I study of bevacizumab added to fluorouracil- and hydroxyurea-based concomitant chemoradiotherapy for poor-prognosis head and neck cancer. J Clin Oncol. 2008;26:1732–41.
Argiris A, Karamouzis MV, Gooding WE, et al. Phase II trial of pemetrexed and bevacizumab in patients with recurrent or metastatic head and neck cancer. J Clin Oncol. 2011;29:1140–5.
Machiels JP, Henry S, Zanetta S, et al. Phase II study of sunitinib in recurrent or metastatic squamous cell carcinoma of the head and neck: GORTEC 2006-01. J Clin Oncol. 2010;28:21–8.
Blumenschein GR, Glisson BS, Lu C, et al. Final results of a phase II study of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic or recurrent squamous cell cancer of the head and neck (SCCHN). J Clin Oncol. 2012;30:15s. Abstract 5592.
Vermorken JB, Peyrade F, Krauss J, et al. Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomized phase I/II ADVANTAGE trial (phase II part). Ann Oncol. 2014;25:682–8.
Cohen EE, Davis DW, Karrison TG, et al. Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study. Lancet Oncol. 2009;10:247–57.
Argiris A, Kotsakis AP, Hoang T, et al. Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 2013;24:220–5.
Gildener-Leapman N, Ferris RL, Bauman JE. Promising systemic immunotherapies in head and neck squamous cell carcinoma. Oral Oncol. 2013;49:1089–96.
Wallis SP, Stafford ND, Greenman J. The clinical relevance of immune parameters in the tumor microenvironment of head and neck cancers. Head Neck. 2015;37:449–59.
Naidoo J, Page DB, Wolchok JD. Immune modulation for cancer therapy. Br J Cancer. 2014;111:2214–9.
Saloura V, Zuo Z, Koeppen H, et al. Correlation of T-cell inflamed phenotype with mesenchymal subtype, expression of PD-L1, and other immune checkpoints in head and neck cancer. J Clin Oncol. 2014;32:5s. Abstract 6009.
Seiwert TY, Burtness B, Weiss J, et al. A phase Ib study of MK-3475 in patients with human papillomavirus (HPV)-associated and non-HPV-associated head and neck (H/N) cancer. J Clin Oncol. 2014;32:5s. Abstract 6011.
Chow LQ, Burtness B, Weiss J, et al. A phase Ib study of pembrolizumab (Pembro; MK-3475) in patients (Pts) with human papilloma virus (HPV)-positive and negative head and neck cancer (HNC). Ann Oncol. 2014;25:v1–41. Abstract LBA31.
Vermorken JB, Psyrri A, MesÃa R, et al. Impact of tumor HPV status on outcome in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: retrospective analysis of the phase III EXTREME trial. Ann Oncol. 2014;25:801–7.
Vermorken J. Extreme (PF+/-cetuximab) and spectrum (PF+/- panitumumab): HPV status and outcome. Radiother Oncol. 2013;106(Suppl1):S2–3.
Argiris A, Li S, Ghebremichael M, et al. Prognostic significance of human papillomavirus in recurrent or metastatic head and neck cancer: an analysis of Eastern Cooperative Oncology Group trials. Ann Oncol. 2014;25:1410–6.
Argiris A, Buchanan A, Brockstein B, et al. Docetaxel and irinotecan in recurrent or metastatic head and neck cancer: a phase 2 trial of the Eastern Cooperative Oncology Group. Cancer. 2009;115:4504–13.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Szturz, P., Vermorken, J.B. (2016). Systemic Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck. In: Bernier, J. (eds) Head and Neck Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-27601-4_42
Download citation
DOI: https://doi.org/10.1007/978-3-319-27601-4_42
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-27599-4
Online ISBN: 978-3-319-27601-4
eBook Packages: MedicineMedicine (R0)