For patients with this type of cancer, one standard treatment option is cetuximab (Erbitux®) + radiation. We wish to study the addition of albumin-bound paclitaxel (Abraxane®) to this standard regimen of cetuximab + radiation. Albumin-bound paclitaxel and cetuximab both are chemotherapy drugs which are administered by vein.

Previous studies have shown that albumin-bound paclitaxel can kill head and neck cancer cells when given alone or in combination with chemotherapy. The purpose of this study is to establish a safe dose range of albumin-bound paclitaxel given in combination with cetuximab and radiation therapy. The investigators want to find out what effects, good and/or bad, the albumin-bound paclitaxel has on you and your head and neck cancer.

Inclusion Criteria:

• Locally and/or regionally advanced head and neck squamous cell carcinoma (AJCC Stage III-IVB)
• Karnofsky performance status ≥ or = to 70%
• Adequate bone marrow function: absolute neutrophil count ≥ or = to 1,500/μl, platelets ≥ or = to 100,000/μl, hemoglobin ≥ or = to 9 gm/dl
• Adequate hepatic function:

Total Bilirubin ≤ or = to institutional upper limit of normal (ULN) AST and ALT and Alkaline Phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST or ALT) should be used

• Patients must have adequate renal function: serum creatinine ≤ 1.5 mg/dl or estimated creatinine clearance of ≥ 45 ml/min by Cockcroft and Gault method
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
• Women of childbearing potential must have a negative pregnancy test
• Patients must have ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Other active malignancy, other than indolent malignancies which the investigator determines are unlikely to interfere with treatment or efficacy analysis. For example, patients with non-melanoma skin cancer, in situ carcinoma of the cervix, or prostate cancer within the no current biochemical (PSA) or radiologic evidence of disease may enroll
• Prior radiation therapy for head and neck cancer
• Patients with multifocal peripheral sensory alterations or paresthesias (including tingling) interfering with function, per patient report (example: activities of daily living)
• Inability to comply with study and/or follow-up procedures
• Women who are pregnant or lactating
• Serious concomitant medical disorders (for example, active infection, uncontrolled seizure disorder, unstable angina, auto-immune connective tissue disease) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study
• History of severe infusion reaction to a monoclonal antibody
• Patients with nasopharyngeal carcinoma are not eligible