• Tolerability [ Designated as safety issue: Yes ]
  
• Overall response rate [ Designated as safety issue: No ]
  
• Failure-free survival [ Designated as safety issue: No ]
  
• Survival [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the tolerability of paclitaxel and carboplatin followed by radiotherapy with or without paclitaxel and carboplatin followed by gefitinib in patients with stage III non-small cell lung cancer.
• Determine the overall response rate, failure-free survival, and survival in patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to CTC performance status (PS) and recent weight loss (PS 2 or PS 0-1 with weight loss of 5% or more within the past 3 months [stratum I] vs PS 0-1 with weight loss less than 5% within the past 3 months [stratum II]).

All patients receive induction therapy comprising paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients then receive therapy based on their assigned stratum.

• Stratum I: Patients receive oral gefitinib once daily for 7 weeks. Patients also undergo concurrent radiotherapy once daily 5 days a week for 7 weeks.
• Stratum II: Patients receive gefitinib and radiotherapy as in stratum I concurrently with paclitaxel IV over 1 hour followed by carboplatin over 30 minutes once weekly for 7 weeks.

Patients are followed every 2 months for 2 years, every 4 months for 2 years, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 18-144 patients (9-72 per stratum) will be accrued for this study within 13 months.

DISEASE CHARACTERISTICS:

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

  • Squamous cell carcinoma
  • Adenocarcinoma (including bronchoalveolar cell)
  • Large cell anaplastic carcinoma (including giant and clear cell carcinoma)

• Unresectable stage IIIA or selected stage IIIB disease

  • T1-2, N2 disease allowed
  • T3, N2 or T4, N0-2 disease allowed if based on closeness to carina, invasion of mediastinum, or invasion of chest wall
  • No T3, N0-1 disease
  • No M1 disease
  • No direct invasion of vertebral body
• Tumors adjacent to a vertebral body allowed if no bone invasion and if all gross disease can be encompassed in radiation boost field
• Contralateral mediastinal disease (N3) allowed if all gross disease can be encompassed in radiation boost field
• No scalene, supraclavicular, or contralateral hilar node involvement

• Transudate, cytologically negative, non-bloody pleural effusion allowed if the tumor can be encompassed in radiotherapy field

  • Pleural effusions seen on chest CT scan but not on chest x-ray that are too small to tap are allowed
  • Pleural effusions appearing only after thoracotomy or other invasive thoracic procedure are allowed

• Measurable disease

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

  • The following are not considered measurable:

    • Pleural effusions
    • Completely resected tumors
    • Ill-defined masses with post-obstructive changes

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• CTC 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin less than 1.5 mg/dL
• AST less than 2 times upper limit of normal
• No chronic liver disease

Renal:

• Creatinine clearance at least 20 mL/min

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other concurrent uncontrolled illness
• No ongoing or active infection
• No other currently active malignancy (must have completed therapy and be at less than 30% risk of relapse to be eligible) except nonmelanoma skin cancer
• No chronic gastrointestinal disorders (e.g., diarrhea or emetic disorders or malabsorptive conditions) that would preclude study participation
• No psychiatric illness or social situation that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for NSCLC
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except steroids for adrenal failure, hormonal therapy for non-disease-related conditions (e.g., insulin for diabetes), or intermittent use of dexamethasone as antiemetic

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy for NSCLC
• No concurrent palliative radiotherapy

Surgery:

• At least 2 weeks since prior formal exploratory thoracotomy

Other:

• At least 7 days since prior CYP3A4 inducers (e.g., phenytoin, carbamazepine, barbiturates, rifampin, dexamethasone, or Hypericum perforatum [St. John's wort])
• No concurrent CYP3A4 inducers
• No concurrent combination antiretroviral therapy in HIV-positive patients