Opinion statement
Head and neck squamous cell carcinoma is now the 8th most common cancer affecting men in the United States largely due to a rising epidemic of oropharynx cancer (tonsil and tongue base) associated with the human papillomavirus (HPV). The median overall survival for recurrent or metastatic head and neck cancer (R/M HNSCC) remains less than 1 year despite modern chemotherapy and targeted agents. Palliative chemotherapy and the epidermal growth factor receptor inhibitor, cetuximab, constitute the backbone of treatment for patients with R/M HNSCC. Platinum doublets studied in phase III trials include cisplatin/5-FU, cisplatin/paclitaxel, and cisplatin/pemetrexed. Platinum chemotherapy in combination with 5-fluorouracil and cetuximab has resulted in the longest median overall survival. Combination platinum regimens increase response rates and toxicity but not survival and should be reserved for patients who are symptomatic from their disease for whom the benefit of a partial response may be worth the cost of increased treatment-related side effects. For many patients who are asymptomatic with a low disease burden, single agent regimens are appropriate to balance treatment with side effects. Drugs commonly used as single agents in the treatment of R/M HNSCC include docetaxel, paclitaxel, cetuximab, capecitabine, pemetrexed, and methotrexate. Best supportive care alone is often appropriate for poor performance status patients. Palliative radiation therapy is beneficial for treating symptomatic metastatic sites. Aggressive symptom management is imperative for all patients and often should include referral to experts in palliative care and pain management. New therapies currently under investigation include mTOR inhibitors, anti-angiogenic agents, and IGF1R inhibitors. Given the poor prognosis for most patients with R/M HNSCC, enrollment in clinical trials investigating novel approaches to therapy should be encouraged.
Similar content being viewed by others
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19):1944.
Gillison ML, Lowy DR. A causal role for human papillomavirus in head and neck cancer. Lancet. 2004;363(9420):1488.
Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007;110(7):1429–35.
Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011. CA: Clin Lung Canc. 2011;61(4):212–36.
Gasco M, Crook T. The p53 network in head and neck cancer. Oral Oncol. 2003;39:222–31.
Smit M, Balm A, Hilgers F, et al. Pain as sign of recurrent disease in head and neck squamous cell carcinoma. Head & Neck. 2001;23:372–5.
Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100:261–9.
Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival in patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.
Urba S, van Herpen CM, Sahoo TP, et al. Phase III study of pemetrexed in combination with cisplatin (pem/cis) versus placebo plus cisplatin (cis) in patients with recurrent or metastatic squamous cell head and neck cancer (HNC). Ann Oncol. 2010;21 suppl 8:viii314.
Morton RP, Rugman F, Dorman EB, et al. Cisplatinum and bleomycin for advanced or recurrent squamous cell carcinoma of the head and neck: a randomized factorial phase III controlled trial. Canc Chemother Pharmacol. 1985;15:283–9.
The Liverpool Head and Neck Oncology Group. A phase III randomized trial of cisplatinum, methotrexate, cisplatinum + methotrexate and cisplatinum + 5-FU in end stage squamous cell carcinoma of the head and neck. Br J Cancer. 1990;61:311–5.
Kish MS, Weaver A, Jacobs J, et al. Cisplatinum and 5-fluorouracil infusion in patients with recurrent and disseminated epidermoid cancer of the head and neck. Cancer. 1984;53:1819.
Jacobs C, Lyman G, Velez-Garcia 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(2):257–63.
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(8):1245–51.
Fury MG, Pfister DG. Current recommendations for systemic therapy of recurrent and/or metastatic head and neck squamous cell cancer. JNCCN. 2011;9:681–90.
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.
Forastiere AA, Shank D, Neuberg D, et al. Final report of a phase II evaluation of paclitaxel in patients with advanced squamous cell carcinoma of the head and neck. Cancer. 1998;82:2270–4.
Smith RE, Thornton DE, Allen J. A phase II trial of paclitaxel in squamous cell carcinoma of the head and neck with correlative laboratory studies. Semin Oncol. 1995;22(3 suppl 6):41–6.
Dreyfuss AI, Clark JR, Norris CM, et al. Docetaxel: an active drug for squamous cell carcinoma of the head and neck. J Clin Oncol. 1996;14:1672–8.
Couteau C, Chouaki N, Leyvraz S, et al. A phase II study of docetaxel in patients with squamous cell carcinoma of the head and neck. Br J Cancer. 1999;81(3):457–62.
Catimel G, Verweij J, Mattijssen V, et al. Docetaxel (Taxotere): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. Ann Oncol. 1994;5(6):533–7.
Catimel G, Vermorken JB, Clavel M, et al. 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;5:543–7.
Samlowski WE, Gundacker H, Kuebler JP, et al. 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;19:311–5.
Sandler A, Saxman S, Bandealy M, et al. Ifosfamide in the treatment of advanced or recurrent squamous cell carcinoma of the head and neck: a phase II Hoosier Oncology Group trial. Am J Clin Oncol. 1998;21(2):195–7.
Cervellino JC, Araujo CE, Pirisi C, et al. Ifosfamide and mesna for the treatment of advanced squamous cell head and neck cancer. A GETLAC study. Oncology. 1991;4892:89–92.
Huber M, Lippman S, Benner S, et al. A phase II study of ifosfamide in recurrent squamous cell carcinoma of the head and neck. Am Journal Clin Oncol. 1996;19(4):379–83.
Martin M, Diaz-Rubio E, Gonzalez Larriba JL, et al. Ifosfamide in advanced epidermoid head and neck cancer. Canc Chemother Pharmacol. 1993;31(4):340–2.
Degardin M, Oliveira J, Geoffrois J, 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.
Saxman S, Mann B, Canfield V, et al. 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(4):398–400.
Testolin A, Recher G, Cristoferi V, et al. Vinorelbine in pre-treated advanced head & neck squamous cell carcinoma. A phase II study. Investig New Drugs. 1994;12(3):231–4.
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.
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(1):85–92.
Burtness BA, Manola J, Axelrod R, et al. A randomized phase II study of ixabepilone (BMS-247550) given daily x 5 days every 3 weeks or weekly in patients with metastatic or recurrent squamous cell carcinoma of the head and neck: an Eastern Cooperative Oncology Group study. Annals Oncol. 2008;19:977–83.
Argiris A, Li Y, Murphy BA, et al. Outcome of elderly patients with recurrent or metastatic head and neck cancer treated with cisplatin-based chemotherapy. J Clin Oncol. 2004;22:262–8.
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, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-α-1,3-galactose. N Engl J Med. 2008;358:1109–17.
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.
Burtness B, Goldwasser MA, Flood W, et al. 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, 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.
Vermorken JB, Stohlmacher J, Davidenko I, et al: Primary efficacy and safety results of SPECTRUM, a phase 3 trial in patients (pts) with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) receiving chemotherapy with or without panitumumab (pmab). ESMO 2010.This abstract reports clinical activity but no survival benefit with the addition of panitumumab to chemotherapy in patients with R/M HNSCC.
Machiels J, 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, randomized phase 3 trial. Lancet Oncol. 2011;12:333–43.
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. Annals Oncology 2011, August 23, epub ahead of print.
Cohen EE, Rosen F, Stadler WM, et al. Phase II trial of ZD 1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol. 2003;21:1980–7.
Stewart JWS, Cohen EEW, 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.
Argiris A, Ghebremichael M, Gilbert J, et al. A phase III randomized, placebo-controlled trial of docetaxel (D) with or without gefitinib (G) in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): A trial of the Eastern Cooperative Oncology Group (ECOG). J Clin Oncol. 2009;27:15s. suppl; abstr 6011.
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.
Seiwert TY, Jagadeeswaran R, Faoro L, et al. The MET receptor tyrosine kinase is a potential novel therapeutic target for head and neck squamous cell carcinoma. Cancer Res. 2009;69:3021–31.
Knowles LM, Stabile LP, Egloff AM, et al. HGF and c-Met participate in paracrine tumorigenic pathways in head and neck squamous cell cancer. Clin Cancer Res. 2009;15:3740–50.
Schmitz S, Kaminsky-Forrett M, Henry S, et al. Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: GORTEC 2008-02. J Clin Oncol. 2010;28(suppl):5500.
Disclosure
No potential conflicts of interest relevant to this article were reported.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Price, K.A.R., Cohen, E.E. Current Treatment Options for Metastatic Head and Neck Cancer. Curr. Treat. Options in Oncol. 13, 35–46 (2012). https://doi.org/10.1007/s11864-011-0176-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11864-011-0176-y