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Concurrent radiation therapy with high dose cisplatin represents the definitive treatment for locally advanced head and neck squamous cell carcinoma (Adelstein, Li et al. 2003);(Bernier, Cooper et al. 2005) who are unresectable unfit or refuse surgery with an associated complete response rate of 40% and median OS of 19.1 months. The results from the two large phase III adjuvant studies confirm that the addition of cisplatin improves loco-regional control and disease-free survival In comparison to radiation alone with mixed results on overall survival.(Bernier, Cooper et al. 2005). However, a separate study by the European Organization of Research and Treatment of Cancer (EORTC) that included 167 patients with LAHNC confirmed that both 5 year PFS (47% vs 36%) and OS (53% vs 40%; HR = 0.70(95% CI 0.52–0.95) favored concurrent CRT over RT alone. (Bernier, Domenge et al. 2004)
In addition to CDDP, cetuximab (Cmab), a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is used in combination with RT in patients with LASCCHN. Bonner et al.(Bonner, Harari et al. 2006) demonstrated that Cmab plus RT significantly improved loco-regional control, PFS, and OS compared with radiation therapy alone. However, Cmab plus RT couldn’t be established to be the standard therapy for LASCCHN, as Cmab plus RT has never been compared with triweekly cisplatin plus RT in a prospectively randomized Phase III study. Furthermore, no prospective trials of Cmab plus RT have been conducted in patients who are not eligible for treatment with CDDP. The study by Bonner et al. included patients with normal organ function, younger age, and high KPS. Regarding toxicity, concurrent Cmab and RT led to a higher number of Grade 3 or 4 skin toxicity than those receiving RT alone (35.1 versus 21.2%, P ; 0.05), although there were few cases of nausea, vomiting, renal impairment and neuro- and ototoxicity (Bonner, Harari et al. 2010). Other studies have also observed Grade 3 or 4 radiation dermatitis in over 30% of patients treated with Cmab plus RT (Giro, Berger et al. 2009, Studer, Brown et al. 2011) . Severe skin reactions could reduce the patient’s quality of life and may sometimes lead to treatment interruption and dose reduction. Taken together, the currently available data do not support the use of Cmab plus RT as an alternative to RT alone in patients who cannot tolerate cisplatin.

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