Inclusion Criteria

Inclusion criteria:

- Patients must have histologically or cytologically confirmed Squamous Cell Cancer of
the oropharynx, hypopharynx or larynx (For patients with oropharynx primary, the
tumor must be negative for p16 by immunohistochemistry).

- Patients with selected Stage III or IV disease (T2 N2-3 M0 or T3-4 any N0
M0)including no distant metastases (T1, any N or T2N1 are not eligible).

- History/Physical examination by a Radiation Oncologist and Medical oncologist prior
to entering the study.

- Examination by an ENT or Head & Neck Surgeon including laryngopharyngoscopy prior to
entering the study.

- Patients must have a chest CT scan, or PET/CT scan to rule out metastatic disease

- Patients must have a CT scan, MRI, or PET/CT scan of the tumor site and neck nodes
prior to entering the study.

- Patients must have an EKG and ECHO or MUGA scan prior to entering the study.

- Patients must have Zubrod Performance Status of 0-1.

- Patients must be ≥ 18 years of age.

- Patients must have normal organ and marrow function as defined below:

- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

- Platelets ≥ 100,000 cells/mm3

- Hemoglobin ≥ 8.0 g/dl

- Serum creatinine < 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min

- Total bilirubin < 2 x the institutional upper limit of normal

- AST or ALT ≤ 3 x the institutional upper limit of normal

- Patient must have magnesium, calcium, glucose, potassium and sodium levels within
normal limits

- Women of childbearing potential must have a negative pregnancy test prior to
registration.

- Patients of reproductive potential must practice effective contraception while on
study and for at least 60 calendar days following treatment.

- All patients must sign an informed consent prior to enrollment.

- Patients must comply with the treatment plan and follow-up schedule.

Exclusion criteria:

- Patients with simultaneous primaries or bilateral tumors.

- Patients who have had gross total excision of the primary tumor.

- Patients with initial surgical treatment, radical or modified neck dissection.

- Patients who received prior systemic chemotherapy for the study cancer.

- Patients who received prior radiotherapy to the region of the study cancer that would
result in overlap of radiation therapy fields.

- Patients with primary tumor of oral cavity, nasopharynx, sinuses or salivary glands.

- Prior allergic reaction to the study drugs.

- Patients who have had prior therapy that specifically and directly targets the
EGFR/HER2 pathway.

- Patients who have current active hepatic or biliary disease (with exception of
patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver
disease per investigator assessment);

- Pregnant women or sexually active patients not willing or able to use medically
acceptable forms of contraceptive method while on treatment.

- Patients with severe, active co-morbidity, defined as follows:

- Uncontrolled cardiac disease, such as uncontrolled hypertension, unstable
angina, and/or congestive heart failure requiring hospitalization within the
last 6 months

- Transmural myocardial infarction within the last 6 months

- Left ventricular ejection fraction < 45%

- Acute bacterial or fungal infection requiring intravenous antibiotics at the
time of registration

- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 calendar days
prior to registration

- Hepatic insufficiency resulting in clinical jaundice and/or Coagulation defects

- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition