Intra-arterial Versus Intravenous Cisplatin, Combined With Radiation, for Oral Cavity and Oropharynx Cancer

Inclusion Criteria:

* Ability to understand and the willingness to sign a written informed consent document
* Histologically or cytologically confirmed stage IV squamous cell carcinoma of the oral cavity or oropharynx staged according to AJCC guidelines
* T4 staged tumor with a tumor volume greater than or equal to 30 cc
* Nodal staging of N0 through 2a
* No evidence of distant metastatic disease, as determined by a negative PET scan or other clinically appropriate means
* Age ≥ 18
* Clinically eligible for both intra-arterial and intravenous administration of cisplatin
* Women of childbearing potential must have a negative pregnancy test.
* Agree to use adequate contraception prior to study entry and for the duration of study participation and for 3 months after study treatment ended
* Biopsiable via a transoral approach
* Life expectancy of at least 5 years
* ECOG performance status ≤ 2
* Measurable disease as defined by RECIST criteria
* Absolute neutrophil count ≥ 1,000/mm3
* Hemoglobin ≥ 8.0 g/dl
* Platelet count ≥ 100,000/mm3
* Leukocytes≥3500/mcL
* Total Bilirubin ≤ ULN of institution performing testing
* Creatinine within normal institutional limits

Exclusion Criteria:

* Radiologic evidence of bone destruction
* Tumor with involvement of cartilage or bone
* Requires bilateral IA infusion with radiologist determination that tumor extends across the midline in excess of 30% of the tumor volume
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents and pre-medications used in the study, including drugs formulated with polysorbate 80
* Allergy to cardiac catheterization contrast agents, in which antihistamines are not sufficient to suppress a reaction or severe enough to pose a significant danger to the subject
* History of stroke, CABG, or significant blockage of carotid arteries or coronary arteries or current blockage of coronary or carotid arteries equal to or in excess of 50% blockage; Interventional radiology must agree that the patient is a good candidate for catheterization.
* Intolerance to IV, IA, or radiation therapy treatment for any reason as determined by the procedural physician
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnancy
* Breast feeding women
* Prior or concurrent non-head and neck malignancies, excluding adequately treated basal or squamous cell cancer of the skin, in situ cervical cancer, stage I or II cancer from which the subject has been in complete remission for at least 12 months, any cancer from which the subject has been cancer free for 5 years
* Tumor site which cannot provide a biopsy in the clinic via punch or core needle biopsy performed
* Second primary head and neck tumor (concurrent or previous head and neck tumor unless it was a basal or squamous cell skin cancer)
* Unknown primary tumor site
* Prior surgery, chemotherapy, biologic or radiotherapy for a head or neck malignancy (excluding minor surgical procedures for skin cancer)
* History of surgery (non-oncologic) in the field of the tumor or treatment bed.
* Participation in an investigational treatment or intervention study within 90 days of screening visit
* calculated creatinine clearance less than 60 mL/min/1.73 m2