Neoadjuvant IRESSA As Single Agent PreopTherapy for NSCLC With Molecular Correlates

DISEASE CHARACTERISTICS:

• Histologically confirmed resectable non-small cell lung cancer (NSCLC), meeting 1 of the following clinical staging criteria:

  • Stage IA or IB (T1-2, N0)
  • Stage II (T1-2, N1 with negative mediastinoscopy or T3, N0)

  • Stage IIIA (T3, N1 with negative mediastinoscopy)

    • Level 10 hilar nodes may be positive provided mediastinoscopy is negative

• The following are not allowed (as evidenced by clinical staging criteria [CT scan, positron-emission tomography (PET) scan, or mediastinoscopy):

  • Positive N2 lymph nodes (ipsilateral/subcarinal mediastinal lymph nodes)
  • Positive N3 lymph nodes (contralateral mediastinal/hilar and supraclavicular/scalene lymph nodes)
  • T4 primary tumor (malignant pleural effusion or mediastinal invasion)
  • Symptomatic tumors (T3, N0-1) involving the superior sulcus (i.e., Pancoast tumors)
• Measurable disease by contrast-enhanced CT scan
• No metastatic disease (except peribronchial or hilar lymph node involvement [N1]) by fludeoxyglucose F 18 PET scan

• No malignant pleural effusion by preoperative evaluation

  • Pleural effusions visible only on CT scan that are not large enough for safe thoracentesis are allowed

  • No exudative effusions (even if cytologically negative), as evidenced by any of the following:

    • Ratio of pleural fluid protein to serum protein > 0.5
    • Ratio of pleural fluid lactic dehydrogenase (LDH) to serum LDH ≥ 0.6
    • Pleural fluid LDH > 200 IU/L
• No superior vena cava syndrome
• No spinal cord compression

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Eastern Cooperative Oncology Group (ECOG) 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 4,000/mm^3
• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 2 times ULN
• Alkaline phosphatase ≤ 2 times ULN

Renal

• Creatinine < 1.5 times ULN

Cardiovascular

• No uncontrolled ventricular arrhythmia
• No myocardial infarction within the past 3 months

Pulmonary

• Pre-resection FEV_1 > 2.0 L OR
• Predicted post-resection FEV_1 > 1.0 L

• No clinically active interstitial lung disease

  • Chronic stable asymptomatic radiographic changes allowed
• No post-obstructive pneumonia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing to provide tumor biopsy pre- and post-gefitinib administration AND undergo PET scan
• No known severe hypersensitivity to study drug or any of its excipients
• No uncontrolled major seizure disorder
• No unstable or uncontrolled diabetes mellitus
• No serious infection requiring IV antibiotics
• No grade 3 neuropathy
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No other unstable or serious medical condition that would preclude study treatment or surgery
• No psychiatric disorder that would preclude giving informed consent
• No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow up
• No other significant clinical disorder or laboratory finding that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior or concurrent systemic chemotherapy for NSCLC

Endocrine therapy

• Not specified

Radiotherapy

• No prior or concurrent radiotherapy for NSCLC

Surgery

• Recovered from prior oncologic or other major surgery
• At least 5 years since prior resection of lung disease
• No prior surgery for NSCLC
• No concurrent ophthalmic surgery

Other

• More than 30 days since prior non-approved or investigational drugs
• No other concurrent therapy for NSCLC
• No other concurrent investigational therapy

• No concurrent use of any of the following medications:

  • Phenytoin
  • Carbamazepine
  • Barbiturates (e.g., phenobarbital)
  • Rifampin
  • Hypericum perforatum (St. John's wort)