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)