Erlotinib and Radiation Therapy in Treating Older Patients With Stage I, Stage II, Stage III, or Stage IV Esophageal Cancer

OBJECTIVES:

Primary

• Assess the overall survival of older patients with stage I-IV squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction treated with erlotinib hydrochloride in combination with radiotherapy.

Secondary

• Assess the proportion of patients achieving mucosal complete response after treatment with this regimen.
• Determine the progression-free survival of patients treated with this regimen.
• Assess the effect of this regimen on dysphagia control, performance status, and overall quality of life of these patients.
• Investigate the correlation between smoking status and overall survival of these patients.
• To correlate the Epidermal growth factor receptor (EGFR) and phosphor Epidermal growth factor receptor (pEGFR) expression by IHC and EGFR mutation status with clinical outcomes.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily for 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo external beam radiotherapy 5 days a week in weeks 1-4 or 5 days a week for the first 5.5 weeks.

Tumor tissue samples are analyzed by IHC for the expression of E-cadherin, P-cadherin, vimentin, cytokeratin, phospho-S6, and Ki67.

After completion of study treatment, patients are followed at 30 days and annually thereafter.

DISEASE CHARACTERISTICS:

• Biopsy-proven primary squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal (GE) junction

• GE junction tumors with 50% or more tumor located in the esophagus determined by radiologic or endoscopic evaluation
• Stage I-IVA disease determined by CT scan or MRI of the chest and abdomen

• Stage IVB disease allowed if metastases to distant regional lymph nodes (celiac or cervical) only and no other sites
• Not a surgical candidate and ineligible for chemotherapy due to any of the following:

• Neuropathy
• Cardiac disease
• Performance status 2
• General overall condition felt by the investigator to be a contraindication to platinum-based therapy
• Bronchoscopy with biopsy and cytology required if primary esophageal cancer is < 26 cm from incisors
• No evidence of clinically active interstitial lung disease (patients who are asymptomatic with chronic, stable, radiographic lung changes allowed)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 4 months
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count > 100,000/mm³
• Bilirubin ≤ 1.3 mg/dL
• ALT and AST ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN
• No prior malignancies except basal cell or squamous cell skin cancer, in situ cervical cancer, or superficial transitional cell bladder cancer, unless diagnosed and/or treated > 2 years prior to current study and are without evidence of recurrence
• No history of allergy to erlotinib or any of its excipients
• No serious, uncontrolled, concurrent infection
• No clinically serious, uncontrolled medical conditions that the investigator feels might compromise study participation
• No lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
• No unwillingness to participate or inability to comply with the protocol for the duration of the study

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy for this tumor
• No prior resection or attempted resection of esophageal cancer
• No prior anti-epidermal growth factor receptor therapy (unless given in an adjuvant setting and completed at least 12 months earlier)
• No participation in any investigational drug study within the past 4 weeks
• No HIV-positive patients receiving antiretroviral therapy
• No concurrent CYP3A4/5 inducers or inhibitors