Induction Chemotherapy Followed by Chemoradiotherapy for Head and Neck Cancer

Given the toxicity of high dose cisplatin, attention has focused on identifying patients at
lower risk for failure who may potentially benefit from less aggressive chemoradiotherapy
approaches. HPV-positive Head and Neck Cancer responds favorably to radiation therapy. This
has prompted investigators to suggest that patients with these cancers might be
"over-treated" and unnecessarily subjected to the toxicity of intensive chemoradiotherapy
with excessively high radiation doses.

This study will select patients with HPV-positive Head and Neck cancer for attenuated therapy
and may have important implications for individualization of care in the future. The regimen
of carboplatin and paclitaxel was selected for the induction chemotherapy phase because of
its ease of administration, improved toxicity profile, high rates of dose delivery, and
excellent published results showing high response rates and overall survival. This study will
use induction chemotherapy primarily as a means to select HPV-positive Head and Neck Cancer
patients, who may benefit from significant radiation dose de-intensification in the
concurrent chemoradiotherapy phase of treatment. The rationale for this risk-adapted approach
to local therapy based on HPV status is to administer effective comprehensive treatment
individualized at diagnosis and after assessment of response to induction chemotherapy (for
patients with HPV-positive tumors), thus avoiding unnecessary and potentially toxic
treatment, and hence optimizing the therapeutic ratio.

Inclusion Criteria:

- Pathologically proven diagnosis of HPV-positive squamous cell carcinoma of the
oropharynx, hypopharynx, or larynx. HPV-positivity will be defined as tumors that are
p16-positive by immunohistochemistry.

- Clinical stage III or IV disease; Note: Patients with M1 tumors are not eligible.

- Appropriate stage for protocol entry, including no distant metastases, based upon
minimum diagnostic workup

- Zubrod Performance Status 0-1

- Age > 18

- Adequate bone marrow function

- Adequate hepatic function

- Adequate renal function

- Pregnancy test within 4 weeks prior to registration for women of childbearing
potential

- Women of childbearing potential and male participants must agree to use a medically
effective means of birth control throughout their participation in the treatment phase
of the study (until at least 60 days following the last study treatment)

- Patient must sign study specific informed consent prior to study entry.

Exclusion Criteria:

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years;

- Patients with simultaneous primaries or bilateral tumors are excluded.

- Patients who present with a cervical lymph node metastasis of unknown primary origin;

- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable;

- Prior radiotherapy that would result in overlap of radiation therapy fields;

- Primary site of tumor of oral cavity, nasopharynx, nasal cavity, paranasal sinuses, or
salivary glands;

- Recurrent head and neck cancer;

- Severe, active co-morbidity

- Pregnant or lactating women or women of childbearing potential and men who are
sexually active and not willing/able to use medically acceptable forms of
contraception; this exclusion is necessary because the treatment involved in this
study may be significantly teratogenic.

- Prior allergic reaction to the study drug(s) involved in this protocol.