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)