RATIONALE: Some tumors need growth factors produced by the body's white blood cells to keep growing. ZD1839 may interfere with the growth factor and stop the tumor from growing. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether chemotherapy is more effective with or without ZD1839 for non-small cell lung cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without ZD1839 in treating patients who have stage IIIB or stage IV non-small cell lung cancer.

OBJECTIVES: I. Compare the 1 year survival rate, time to worsening of disease related symptoms, and progression free survival in chemotherapy naive patients with stage IIIB or IV non-small cell lung cancer treated with one of two doses of ZD 1839 or placebo combined with gemcitabine and cisplatin.

PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study. Patients are randomized to one of three treatment arms. Patients receive gemcitabine and cisplatin combined with lower dose oral ZD 1839 (arm I), higher dose oral ZD 1839 (arm II), or placebo (arm III).

PROJECTED ACCRUAL: A total of 1,029 patients (343 per arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven non-small cell lung cancer; Stage III disease that is not curable with surgery or radiotherapy OR Stage IV disease
• Chemotherapy naive

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: See Disease Characteristics
• Endocrine therapy: No concurrent systemic endocrine therapy that is known to have an effect on non-small cell lung cancer
• Radiotherapy: See Disease Characteristics; Prior localized irradiation allowed
• Surgery: See Disease Characteristics; Prior surgery allowed
• Other: No concurrent drugs with known significant cytochrome P450 3A4 inhibitory effects (e.g., ketoconazole, itraconazole, troleandomycin, erythromycin, diltiazem, verapamil)

--Patient Characteristics--

• Age: 18 and over
• Performance status: 0-2
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 2,000/mm3; WBC at least 4,000/mm3
• Hepatic: ALT and AST less than 2.5 times upper limit of normal (ULN) (less than 5 times ULN if liver metastasis present); Bilirubin less than 1.25 times ULN
• Renal: Creatinine less than 1.5 times ULN; Creatinine clearance greater than 60 mL/min
• Cardiovascular: No evidence of severe or uncontrolled cardiovascular disease
• Pulmonary: No evidence of severe or uncontrolled pulmonary disease