Nicotine Levels With Response Rates to Radiation Alone or With Chemo In Head & Neck Cancer

The exposure to tobacco related carcinogens is highly dependent upon dose as well as
interindividual characteristics of metabolism. Risk assessment of carcinogenic profiles for
nicotine and its individual metabolites is complicated by interindividual variations in
nicotine metabolism associated with quantitative nicotine exposure, gender, genetic
polymorphisms, and behavioral and environmentally induced differences in nicotine
metabolizing enzyme activities. Consequently, differences in smoking behavior or tobacco use
have been correlated to differences in nicotine metabolism resulting in cessation strategies
based upon tobacco use, nicotine dependence, and behavioral modification. Cotinine has been
shown to be a reliable marker of nicotine exposure and more reflective of recent rather than
acute nicotine use with better assessment of baseline nicotine levels. Therefore, subjects
will have blood samples drawn weekly during radiation for cotinine analysis.

Radiation therapy efficacy is known to be dependent on tissue oxygen status. Since
therapeutic treatment is less efficacious in patients with poorly vascularized/ hypoxic
tumors, it is desirable to identify and target such patients for special treatment. Recent
magnetic resonance imaging and computed tomography investigations have shown that there are
significant blood flow changes during radiation or chemo-radiation therapy, suggesting that
early blood flow may have prognostic value. Among those methods for oxygen and blood flow
measurements, the near-infrared spectroscopy (NIRS) is more benefit with merit of
non-invasive, portable, fast test, and inexpensive. Our instrument system combined
near-infrared diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy
(DCS) is capable of monitoring tissue oxygen and blood flow simultaneously. This hybrid
diffuse optical instrument has already been used for monitoring of therapeutic effects (e.g.,
radiation therapy, chemotherapy) in tumors in human head & neck and breast. In this study, we
will use this hybrid instrument to investigate the hemodynamic responses to different
therapies (radiation alone, radiation + chemotherapy) in patients with different nicotine
levels. Baseline measurement of tissue oxygen saturation, total hemoglobin concentration and
blood flow using a hybrid optical instrument (DRS for oxygen measurement and DCS for blood
flow measurement). A hand-hold optical probe connected to the hybrid instrument will be
placed on the head/neck tumor for about 3-5 minutes, then move it on the normal arm muscle
for control purposeTumor oxygenation and flow measurements will be performed at the beginning
of every week during the treatment period. During this monitoring process non-invasive blood
pressure monitoring will also occur. Weekly optical measurements will be obtained during
treatment.In this study we will investigate the hemodynamic responses to different nicotine
levels and different therapies (radiation alone, radiation + chemotherapy).

Inclusion Criteria:

- A: Male or female aged 18 or older

- B: Pathologically confirmed squamous cell carcinoma

- C: Measurable disease using CT, MRI, or panendoscopy

- D: Tumor sites to include:

Oropharynx Hypopharynx Oral cavity Larynx Measurable disease with no evidence of primary

- E: Patients to be treated with radiotherapy or chemoradiotherapy as a primary
treatment modality. Patients to be treated with radiotherapy in combination with
platinum based chemotherapy will be considered for enrollment.

- F: Nutritional status to include patients that do not require placement of a feeding
tube as well as patients that are feeding tube dependent. However, patients requiring
total parenteral nutrition prior to initiation of treatment will be excluded.

- G: ECOG performance status of 0, 1 or 2.

- H: Standard of care chemotherapy inclusion criteria to include:

i: No evidence of active angina pectoris or ventricular arrhythmia's; no myocardial
infarction within the last six months. (Patients with medically controlled
hypertension or congestive heart failure are eligible.) ii: Absolute neutrophil count
of > 1000/uL and platelet count > 100,000/uL iii: Serum total bilirubin < 1.5 mg/dL
iv: Creatinine Clearance greater than 60 ml/min creatinine clearance to be calculated
using the formula: (140 - age) x (wgt in kg) * (serum creatinine) x (72)

* multiply by 0.85 for females v: If a pre-existing grade I neuropathy exists,
patients must be willing to risk worsening neuropathy secondary to treatment. Patients
with grade II or greater neuropathy will be excluded from study.

- I: Standard of care treatment will require counseling against the use of tobacco
products and can include nicotine replacement at the request of the patient and
discretion of treating physician. Patients who continue to use tobacco products as
well as patients using any form of cessation strategy (nicotine replacement,
bupropion, or other) will be eligible for enrollment.

- J: Patients enrolled on experimental studies will be considered for enrollment with
final selection to be made by Dr. Kudrimoti, Dr. Warren, Dr. Arnold, and Dr.
Valentino.

- K: Ability to give informed consent

Exclusion Criteria:

- A: Pregnant females. Males and females of childbearing potential must use effective
contraception in order to prevent pregnancy during therapy.

- B: Histology other than squamous cell carcinoma

- C: Patients without measurable disease using CT, MRI, or panendoscopy

- D: Patients eligible for surgical resection alone or with significant (> 25%) surgical
tumor debulking prior to radiotherapy will not be considered for enrollment.
Furthermore, patients who are otherwise not candidates for radiotherapy at the
discretion of the treating physician will be excluded from enrollment.

- E: Patients with a history of previous or current malignancy at other sites diagnosed
within the last 5 years, with the exception of adequately treated carcinoma in-situ of
the cervix or basal or squamous cell carcinoma of the skin. Patients with a history of
other malignancies, who remain free of recurrence or metastases for greater than five
years are eligible.

- F: Patients with active infection will not be eligible for this protocol until the
infection is treated and the symptoms have clinically resolved.

- G: Prior chemotherapy, prior irradiation or surgery for SCCHN will not be allowed.

- H: Patients with metastatic disease will not be eligible for this study.

- I: Patients with grade II or greater peripheral neuropathy will be excluded from
study.

- J: Patients receiving medication to prevent mucositis (palifermin, amifostine, or
other).

- K: Patients requiring total parenteral nutritional support prior to the initiation of
treatment will not be eligible for study.