3'-Deoxy-3'-[18F] Fluorothymidine and Fludeoxyglucose F 18 PET Scans in Evaluating Response to Cetuximab, Cisplatin, and Radiation Therapy in Patients With Advanced Cancer of the Oropharynx, Larynx, or Hypopharynx

OBJECTIVES:

Primary

- To assess whether 3'-deoxy-3'-[18F] fluorothymidine (FLT) and fludeoxyglucose F 18 (FDG)
PET scans can be used to identify patients with advanced squamous cell carcinoma of the
oropharynx, larynx, or hypopharynx who have a biochemical response after 2 weeks of
induction therapy with cetuximab.

- To assess whether FLT and FDG PET imaging-based response after 20-30 Gy of radiotherapy
is predictive of disease control at 6 months after completion of therapy.

Secondary

- To assess whether FLT and FDG PET imaging-based response after cetuximab therapy and/or
20-30 Gy of radiotherapy is predictive of pathologic complete response in these
patients.

- To assess whether FLT and FDG PET imaging-based response after cetuximab therapy and/or
20-30 Gy of radiotherapy is predictive of disease-free survival at 2 years in these
patients.

- To correlate suppression of FLT uptake after cetuximab therapy with thymidine kinase 1
activity and/or expression, proliferation, microvessel density, apoptosis, and signaling
pathway analyses.

- To correlate suppression of FDG uptake after cetuximab therapy with expression of
hexokinases, glucose transporter proliferation, microvessel density, apoptosis, and
signaling pathway analyses.

- To test and refine the ability of a novel commercial software package to quantify
treatment-induced structural and functional/molecular volumetric and sub-volumetric
change.

- To develop a working method for expressing change and predicting outcome.

OUTLINE: Patients receive cetuximab IV on days 1 and 8 of course 1. Beginning in course 2 and
all subsequent courses, patients receive cetuximab IV and cisplatin IV over 2 hours on day 1
and undergo radiotherapy once daily 5 days a week for 7 weeks. Treatment repeats every 7 days
for a total of 8 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo 3'-deoxy-3'-[18F] fluorothymidine and fludeoxyglucose F 18 (FDG) PET scans
at baseline, after the second dose of cetuximab, after 20-30 Gy of radiotherapy, and then at
6 weeks and 6 months after completion of radiotherapy.

Patients undergo tumor tissue biopsies at baseline and after the first dose of cetuximab for
correlative laboratory studies. Samples are analyzed for proliferation (Ki-67 labeling
index), microvessel density (CD-31 staining), apoptosis (TUNEL assay and caspase-3 by IHC)
signaling pathway (expression of EGFR, AKT, and MAPK by IHC), molecules affecting FDG uptake
(expression of GLUT1, GLUT3, and hexokinase by IHC), and thymidine kinase 1 activity or
expression.

After completion of study treatment, patients are followed every 3 months for up to 5 years.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx,
larynx, or hypopharynx

- Advanced disease

- Requires chemoradiotherapy

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy ≥ 16 weeks

- Weight loss ≤ 10% within the past 3 months

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST ≤ 3 times ULN

- Hemoglobin ≥ 8 g/dL

- Creatinine clearance ≥ 40 mL/min

- No peripheral neuropathy ≥ grade 2

- No NYHA class III-IV heart disease

- No uncontrolled infection

- No poorly controlled diabetes that would limit the ability to obtain reliable
fludeoxyglucose F 18 PET scan results

- No other severe underlying disease that, in the judgment of the investigator, would
preclude study participation

PRIOR CONCURRENT THERAPY:

- More than 2 weeks since prior major surgery and recovered

- No prior radiotherapy to the planned treatment field

- No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)