A Phase II Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Erlotinib, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck
A Phase II Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Erlotinib, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib together with docetaxel and radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well erlotinib given together with docetaxel and radiation therapy works in treating patients with stage III or stage IV squamous cell carcinoma of the head and neck.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Patients receive oral erlotinib hydrochloride once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. Beginning on week 3, patients receive docetaxel IV over 1 hour once a week and radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.
At 6-8 weeks after completion of chemoradiotherapy, patients with N2 or greater cervical lymph node involvement at baseline or with residual disease may undergo surgery. Patients with persistent disease during study therapy undergo salvage surgery 6-12 weeks after completion of chemoradiotherapy.
Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR.
After completion of study therapy, patients will be evaluated every 4-8 weeks for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then once a year thereafter.
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed locally advanced squamous cell carcinoma of the head and neck
Stage III or IV disease
Measurable disease (according to RECIST)
No salivary gland and paranasal sinus squamous cell carcinoma
No known brain metastases or direct cerebral invasion by tumor
PATIENT CHARACTERISTICS:
ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
Life expectancy > 12 weeks
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥10 g/dL
Total bilirubin normal
Alkaline phosphatase AND AST and ALT meeting the following criteria:
Creatinine normal OR creatinine clearance ≥ 60 mL/min
No clinically significant heart disease including any of the following:
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride or docetaxel, including other drugs formulated with polysorbate 80
No pre-existing peripheral neuropathy ≥ grade 2
No uncontrolled concurrent illness including, but not limited to, any of the following:
No HIV positivity
No other prior malignancy except for any of the following:
Not poorly compliant
PRIOR CONCURRENT THERAPY: