Reduced-intensity Therapy for Oropharyngeal Cancer in Non-smoking HPV-16 Positive Patients

The investigators have shown in past experience a high success in getting rid of
oropharyngeal cancer (tonsil or base of tongue cancer) using chemotherapy and radiation
therapy in patients who have not smoked, or only smoked a minimal amount of cigarettes or
equivalent. In these patients, the cancer is thought to be caused by a virus (Human Papilloma
Virus, or HPV). HPV is a virus that infects the epidermis (outermost layer of skin) and
mucous membranes of humans. In general, patients with HPV-related cancer such as yours have a
better prognosis compared with patients whose tumors are smoking-related. Taking into account
the good prognosis, it is possible that reducing the intensity of therapy will not affect the
high rate of tumor control, while reducing the side-effects of therapy. In this study, the
investigators plan to reduce the intensity of treatment by replacing the currently used
chemotherapy drugs with an FDA approved drug, cetuximab, which is a monoclonal antibody to a
growth factor which helps cancer cells grow. By opposing the effect of the growth factor,
cetuximab may help radiotherapy kill cancer cells without a lot of effect on the normal
tissue. It differs from chemotherapy in its more selective activity against tumors compared
to normal tissue Cetuximab has the chance to preserve the high rate of success in killing the
tumor but may reduce the side effects and complications of therapy in comparison to
chemotherapy drugs.

The investigators would also like to know if taking cetuximab has any effect on certain
cancer-related molecules in the cancer and the normal cells inside the cheek. They would like
to test this by taking a small biopsy of the tumor, as well as a swab of the inside of the
cheek, before and shortly after the start of therapy.

Inclusion Criteria:

- Patients must have pathologically-confirmed, previously untreated,stage
III-IV(excluding N3 or T4) squamous cell carcinoma of the oropharynx, without evidence
of distant metastasis

- Pretreatment tumor biopsy with sufficient tumor for HPV or p16 analysis is required.
The tumor must be HPV(+) or p16(+)

Smoking history <10 pack-year or equivalent (including cigarettes, cigars, pipes, chewing
tobacco, and/or marijuana). One cannabis joint is equivalent to 5 cigarettes. (Aldington
etal, Thorax 2007; 62:1058-1063). Smoking status definitions (National Health Interview
Survey and Behavioral Risk Factor Surveillance System (Nelson DE etal al, Am J Pub Health
2003;93:1335):

- Smokers: smoking now every day or some days in past month

- Quitters: at least 100 cigarettes/lifetime and not smoking in the past 1-12 months

- Former smoker: at least 100 cigarettes/lifetime and not smoking >12 months

- Never smokers: <100 cigarettes (or equivalent)/lifetime

- KPS > 80 (see Appendix A)

- Patients must undergo pre-treatment endoscopic tumor staging and PET-CT scanning

- Laboratory criteria:

- WBC > 3500/ul

- granulocyte > 1500/ul

- Platelet count > 100,000/ul

- Total Bilirubin < 1.5 X ULN

- AST and ALT < 2.5 X ULN

- Creatinine clearance >30 cc/min

- Patients must sign study specific informed consent

- Patients must have, in the opinion of a treating physician, tumor that is
accessible to biopsy in the clinic.

Exclusion Criteria:

- Prior head and neck malignancy or history of other prior non-head and neck malignancy
(excluding skin cancer and early stage treated prostate cancer) within the past 3
years

- Prior head and neck radiation or chemotherapy

- Any medical or psychiatric illness, which in the opinion of the principal
investigator, would compromise the patient's ability to tolerate this treatment or
limit compliance with study requirements

- Patients residing in prison

- Patients with prior anti-epidermal growth-factor receptor antibody therapy (antibody
or small molecule)