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Correlative Study of Nicotine Levels With Response Rates to Therapy Using Radiation Alone or in Combination With Chemotherapy in Head and Neck Cancer

18 Years
Open (Enrolling)
Larynx Cancer, Lip Cancer, Oral Cavity Cancer, Pharyngeal Cancer, Oropharyngeal Cancer

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Trial Information

Correlative Study of Nicotine Levels With Response Rates to Therapy Using Radiation Alone or in Combination With Chemotherapy in Head and 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

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 +

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.

- 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

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

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

Type of Study:


Study Design:

Observational Model: Case-Only, Time Perspective: Prospective

Outcome Measure:

Correlation of serum cotinine with volumetric response

Outcome Description:

RECIST criteria will be used as a correlate for standardization of tumor response. Volumetric analysis may provide better assessment of bulky tumor size that may have a large necrotic or hypoxic component that may be resistant to treatment. Furthermore, volumetric analysis has been associated with a higher rate of concordance to response based upon RECIST criteria.

Outcome Time Frame:

2 years from start of treatment

Safety Issue:


Principal Investigator

Mahesh Kudrimoti, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Kentucky


United States: Institutional Review Board

Study ID:




Start Date:

August 2007

Completion Date:

December 2015

Related Keywords:

  • Larynx Cancer
  • Lip Cancer
  • Oral Cavity Cancer
  • Pharyngeal Cancer
  • Oropharyngeal Cancer
  • Laryngeal Neoplasms
  • Head and Neck Neoplasms
  • Mouth Neoplasms
  • Lip Neoplasms
  • Oropharyngeal Neoplasms
  • Pharyngeal Neoplasms



Markey Cancer CenterLexington, Kentucky  40536