Vol 6, No 5 (2010)
Review paper
Published online: 2011-01-19
Anti-EGFR targeted therapy for squamos cell head and neck cancer
Onkol. Prak. Klin 2010;6(5):264-271.
Abstract
Standards of radical treatment for squamous cell head and neck cancer (SCHNC) were changed during
last decade. Concomitant radiochemiotherapy became a treatment of choice for locally advanced
SCHNC. This method in comparison with radiotherapy alone produces significant benefit in overall survival.
However, concomitant radiochemotherapy carries high risk of early and late toxicity. This method
is beneficial for a limited subgroup of patients. In this situation, investigation of new therapeutic strategies
is necessary. Currently, probably the most attractive radical treatment strategy is targeted therapy
combined with traditional methods like radiotherapy or radiochemotherapy. Similarly, targeted therapy
is the most promising method of treatment for recurrent or metastatic SCHNC. The most recognized and
well investigated target of molecular treatment for SCHNC is epidermal growth factor receptor (EGFR). EGFR signaling pathway activation is associated with tumor progression and stimulation of chemo- and
radioresistance. EGFR expression is observed in nearly 100% of SCHNC. The most investigated in
advanced clinical trials inhibitor of the EGFR is cetuximab a monoclonal antibody. Randomized phase
III clinical trial showed that addition of cetuximab to radiation therapy improves survival in patients with
locally advanced SCHNC without escalation of radiation-related toxicity. Recently another randomized
trial showed that combination of cetuximab with traditional chemotherapy improves overall survival in
patients with recurrent or metastatic SCHNC. Many others targeted therapy strategies and drugs are
now under investigations. In this paper current indications, limitations and perspectives of the anti-EGFR
targeted therapy for SCHNC are discussed.
Onkol. Prak. Klin. 2010; 6, 5: 264–271
Keywords:
squamous cell head and neck cancerSCHNCEGFRcetuximab
References
- Denis F, Garaud P, Bardet E, et al. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 2004; 22(1): 69–76.
- Brizel DM, Albers ME, Fisher SR, et al. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med. 1998; 338(25): 1798–1804.
- Bernier J, Domenge C, Ozsahin M, et al. European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004; 350(19): 1945–1952.
- Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003; 349(22): 2091–2098.
- Pignon JP, Bourhis J, Domenge C, et al. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 2000; 355(9208): 949–955.
- Pignon JP, le Maître A, Maillard E, et al. MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009; 92(1): 4–14.
- 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): 1245–1251.
- Jacobs C, Lyman G, Velez-García 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): 1257–1265.
- 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(24): 7350–7356.
- Robert F, Ezekiel MP, Spencer SA, et al. Phase I study of anti--epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. J Clin Oncol. 2001; 19(13): 3234–3243.
- Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006; 354(6): 567–578.
- Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010; 11(1): 21–28.
- Wirth LJ, Allen AM, Posner MR, et al. Phase I dose-finding study of paclitaxel with panitumumab, carboplatin and intensity-modulated radiotherapy in patients with locally advanced squamous cell cancer of the head and neck. Ann Oncol. 2010; 21(2): 342–347.
- Gregoire V., Hamoir M., Chen C. i wsp. Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: a phase II, double – blind, placebo-controlled study. 2nd ICHNO Congress, Barcelona 2009 (prezentacja ustna).
- Harrington KJ, El-Hariry IA, Holford CS, et al. Phase I study of lapatinib in combination with chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck. J Clin Oncol. 2009; 27(7): 1100–1107.
- Burtness B, Goldwasser MA, Flood W, et al. 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(34): 8646–8654.
- Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008; 359(11): 1116–1127.
- Mesía R, Rivera F, Kawecki A, et al. Quality of life of patients receiving platinum-based chemotherapy plus cetuximab first line for recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 2010; 21(10): 1967–1973.
- 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(24): 5578–5587.
- Vermorken JB, Stohlmacher J, Dawidenko I, et al. An analysis of safety in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without panitumumab in phase III clinical trial SPECTRUM. . J. Clin. Oncol. 2009; 27(supl.): abstr. 6050.
- 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(16): 2171–2177.
- 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(24): 5568–5577.
- Stewart JS, 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 [corrected]. J Clin Oncol. 2009; 27(11): 1864–1871.
- Argiris M, Ghebremichael J, Gilbert B, et al. A phase III randomized placebo-controlled trial of docetaxel with or without gefitinib in recurrent or metastatic squamous cell carcinoma of the head and neck; a trial of Eastern Cooperative Oncology Group. . J. Clin. Oncol. 2009; 27(supl.): abstr. 6011.
- de Souza JA, Davis DW, Zhang Y, 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(3): 247–257.
- Gibson MK, Kies M, Kim S, et al. Cetuximab and bevacizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an updated report. J Clin Oncol. 2009; 27(supl.): 6049.