Published reports suggest that approximately one quarter to one third of advanced head and neck cancer patients treated with surgery and postoperative radiation therapy experience locoregional disease recurrence. Efforts to diminish these recurrence rates have focused primarily on combined chemoradiation in the postoperative setting. Two recent Phase III cooperative group studies have addressed this precise question. Both studies (RTOG 95-0112 and EORTC 22931) randomized postoperative head and neck cancer patients to radiation alone or radiation in combination with cisplatin chemotherapy.12,13,14 These two randomized trials yielded positive results for their respective endpoints but contrasting results for overall survival.

The EORTC trial enrolled 334 patients and identified a clear benefit in locoregional disease control, disease free survival (primary endpoint) and overall survival for those patients receiving cisplatin chemotherapy concurrent with radiation. The RTOG trial enrolled 459 patients and identified a clear benefit in locoregional disease control (primary endpoint) but not for overall survival with the addition of cisplatin. Both trials confirmed greater acute and overall toxicity with the addition of cisplatin chemotherapy. Therefore, it remains somewhat unclear whether the addition of cisplatin chemotherapy to postoperative radiotherapy for advanced head and neck cancer patients is routinely warranted. Further data maturation for both trials is ongoing. This protocol is therefore designed to examine the addition of a promising new class of molecular growth inhibitor (C225: cetuximab) delivered in conjunction with adjuvant chemoradiation therapy for advanced head and neck cancer patients. In this Phase II setting, C225 will be combined with radiation in conjunction with either cisplatin or docetaxel at relatively low weekly doses in an effort to enhance locoregional disease control.

The epidermal growth factor receptor (EGFR) represents a particularly promising molecular target for modulation regarding the growth and spread of squamous cell carcinomas of the head and neck. In fact, among human solid tumors, the highest frequency of EGFR overexpression is found in squamous cell carcinomas of the head and neck. The knowledge that some 85% - 100% of head and neck squamous cell carcinomas robustly express EGFR has justified the rationale for not performing a priori testing of EGFR expression for patient selection in head and neck cancer trials which incorporate the use of EGFR inhibitors.