To evaluate, using a random assignment phase II design, two treatment regimens that utilize the EGFR inhibitor C225 in combination with chemoradiation in high-risk postoperative head and neck patients. This trial is designed to determine if either regimen is promising enough to be pursued in a subsequent phase III study. This decision will be primarily based on whether there is improvement in disease-free survival relative to the RTOG database of similar patients treated with chemoradiation in the completed intergroup trial RTOG 9501.

Pathologic stage III or IV (note that the preoperative clinical stage may be I-IV if nodes are not appreciated) squamous carcinoma of the head and neck (site of tumor origin oral cavity, oropharynx, larynx, or hypopharynx) following gross total resection and requiring postoperative XRT for high-risk features