Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

OBJECTIVES:

I. To assess whether maintenance therapy with ZD1839 as compared to placebo following induction cisplatin/etoposide/radiotherapy plus consolidation docetaxel improves overall survival and progression-free survival in patients with unresectable Stage III non-small cell lung cancer (NSCLC).

II. To describe the toxicity profile of long term administration of ZD1839. III. To obtain samples for correlative studies.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to performance status (0 vs 1), stage (stage IIIA vs IIIB), measurability of lesion (measurable vs nonmeasurable), and histologic subtype (squamous vs nonsquamous).

Patients receive induction therapy comprising cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Beginning within 24 hours after starting chemotherapy, patients receive concurrent induction radiotherapy 5 days a week for 5 weeks and then boost radiotherapy 5 days a week for 1.5 weeks.

Beginning approximately 4-8 weeks after completion of chemoradiotherapy, patients with stable or responding disease receive consolidation therapy comprising docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 3 courses.

Patients with stable or responding disease are randomized to one of two treatment arms for maintenance therapy. Patients begin maintenance therapy approximately 4-7 weeks after completion of consolidation therapy.

Arm I: Patients receive oral gefitinib daily.

Arm II: Patients receive oral placebo daily. In both arms, maintenance therapy continues for a maximum of 5 years in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for 5 years and then annually for 5 years.