Gemcitabine, Cisplatin, and Gefitinib in Treating Patients Who Are Undergoing Surgery for Stage III Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

• Determine the therapeutic activity of neoadjuvant induction therapy comprising gemcitabine, cisplatin, and gefitinib in patients with stage IIIA non-small cell lung cancer undergoing surgery.

Secondary

• Determine the safety profile of this regimen in these patients.
• Determine the stage downsizing and complete resectability rate in patients with no progressive disease who undergo surgery after treatment with this regimen.

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

Patients receive induction therapy comprising gemcitabine IV over 30 minutes on days 1, 8, 22, 29, 43, and 50; cisplatin IV over 3-6 hours on days 2, 23, and 44; and oral gefitinib once daily on days 51-79. Treatment continues in the absence of disease progression or unacceptable toxicity. Within 2-7 days after completion of induction therapy, patients with no progressive disease undergo tumor resection.

After completion of study treatment, patients are followed at least every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed primary non-small cell lung cancer (NSCLC)

• Clinical stage IIIA by chest CT scan
• Unresectable N2 disease by mediastinoscopy, mediastinotomy, thoracotomy, or video-assisted thoracic surgery
• Measurable disease

• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• Planning to undergo lobectomy or pneumonectomy after induction therapy
• No N3 or metastatic disease by physical exam, thoracic CT scan, bone scan, and CT scan or ultrasound of the liver and adrenal glands
• No pleural or pericardial effusion
• No superior vena cava syndrome
• No diffuse interstitial pulmonary fibrosis
• No signs or symptoms of CNS involvement

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3

Hepatic

• AST and ALT ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin normal
• Alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.25 times ULN
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No medically uncontrolled congestive heart failure or angina pectoris
• No uncontrolled hypertension or arrhythmia
• No myocardial infarction within the past year

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• Physically and mentally fit to receive gemcitabine- and cisplatin-containing chemotherapy
• Physiologically fit to undergo surgery
• No uncontrolled, active infection requiring IV antibiotics
• No history of hypersensitivity to gefitinib or any of its excipients
• No motor or sensory neurotoxicity ≥ grade 2
• No other primary malignancy within the past 5 years except carcinoma in situ of the cervix or adequately treated basal cell skin cancer

• No prior melanoma, breast cancer, or renal cell cancer
• No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy

Chemotherapy

• No prior chemotherapy for NSCLC
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent antiestrogen therapy
• Concurrent replacement steroids and antiemetic steroids allowed

Radiotherapy

• No prior radiotherapy for NSCLC

Surgery

• See Disease Characteristics
• No prior surgery for NSCLC

Other

• More than 1 month since prior and no concurrent investigational agents
• No other prior therapy for NSCLC
• No concurrent CYP3A4 inducers, including any of the following:

• Phenytoin
• Carbamazepine
• Rifampin
• Barbiturates (e.g., phenobarbital)
• Hypericum perforatum (St. John's wort)
• No concurrent systemic retinoids
• No other concurrent antitumor therapy