Adjuvant Erlotinib After Completing Chemoradiotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

OBJECTIVES:

Primary

• Determine the recommended dose of adjuvant erlotinib after the completion of chemoradiotherapy in patients with stage III, IVA, or IVB squamous cell carcinoma of the head and neck.
• Determine the toxicity of this drug in these patients.
• Determine the effects of this drug on plasma and urinary angiogenic factors (specifically vascular endothelial growth factor receptor [VEGFR], VEGFR1, VEGFR2, and basic fibroblast growth factor levels) in these patients.
• Compare the disease-free survival of patients treated with this drug after chemoradiotherapy vs historical control patients treated with chemoradiotherapy alone.
• Correlate levels of angiogenic factors with initial blood vessel concentration in the tumor and the presence or absence of EGFRvIII mutation in patients treated with this drug.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive oral erlotinib once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 8 patients are treated at that dose level.

Patients are followed at 4 weeks, every 12 weeks for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 6-20 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the head and neck

• Stage III, IVA, or IVB
• Must have completed cisplatin- or carboplatin-based chemoradiotherapy within the past 4-12 weeks

• Prior radiotherapy must have been given with a radical intent with receipt of at least 90% of planned dose
• No evidence of disease or presence of inoperable minimal residual disease, defined by 1 of the following:

• Complete response at primary tumor site and nodes (with or without nodal surgery after chemoradiotherapy)
• Negative lymph node status (by physical or radiological exam) AND persistent tumefaction less than 25% of original tumor size or residual mass due to scarring
• Tumor tissue samples available for EGFRvIII mutation analysis
• No known brain metastasis

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• ALT/AST < 2 times upper limit of normal (ULN)
• Bilirubin < ULN (unless due to Gilbert's syndrome)

Renal

• Creatinine < 1.5 times ULN

Cardiovascular

• No myocardial infarction within the past year
• No cardiac ventricular arrhythmias requiring medication
• No history of cardiac disease
• No uncontrolled high blood pressure
• No unstable angina
• No congestive heart failure

Ophthalmic

• No history of severe dry eye syndrome, Sjögren's syndrome, or keratoconjunctivitis sicca
• No severe exposure keratopathy
• No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
• No abnormal corneal sensitivity test (Schirmer test or similar tear production test)
• No disorder that might increase the risk for epithelium-related complication (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis)
• No congenital abnormality (e.g., Fuch's dystrophy)
• No ocular inflammation or infection

Gastrointestinal

• Able to take oral medication
• No gastrointestinal (GI) tract disease requiring IV alimentation
• No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
• No active peptic ulcer disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious active infection
• No other serious underlying medical condition that would preclude study participation
• No prior allergic reaction to compounds of similar chemical or biological composition to erlotinib
• No other malignancy with the past 5 years except adequately treated non-melanoma skin cancer (unless in the same area treated with radical radiotherapy) or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• Recovered from prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• Recovered from prior radiotherapy

Surgery

• See Disease Characteristics
• No prior surgical procedure affecting absorption
• No concurrent ophthalmic surgery

Other

• More than 4 weeks since other prior investigational drugs
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• Concurrent oral anticoagulants (e.g., warfarin) allowed provided there is increased vigilance with respect to INR
• Concurrent nasogastric or gastrostomy tube feeding for dysphagia allowed provided there is no evidence of significant residual mucositis (i.e., > grade 1)