OBJECTIVES:

• Compare the overall survival of patients with stage IIIA or IIIB non-small cell lung cancer treated with induction chemotherapy followed by radiotherapy with or without efaproxiral.
• Compare time to progression, response rate, and pattern of failure of patients treated with these regimens.
• Determine the safety of efaproxiral in these patients.
• Determine the pharmacokinetics of efaproxiral in these patients.
• Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to chemotherapy regimen, Karnofsky performance status (70-80% vs 90-100%), and disease stage (IIIA vs IIIB).

• Induction therapy phase: Patients receive 1 of the following induction chemotherapy regimens:

  • Paclitaxel and carboplatin: Patients receive paclitaxel IV and carboplatin IV on day 1. Treatment repeats every 21 days for a total of 2 courses.
  • Cisplatin and gemcitabine: Patients receive cisplatin IV on day 2 and gemcitabine IV on days 1, 8, and 15. Treatment repeats every 28 days for a total of 2 courses.
  • Cisplatin and vinorelbine: Patients receive cisplatin IV on day 1 and vinorelbine IV on days 1, 8, and either 15 or 22. Treatment repeats every 28 days for a total of 2 courses.

• Randomized phase: Within 42 days after completion of chemotherapy, patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive efaproxiral IV over 30-45 minutes with supplemental oxygen and then undergo concurrent radiotherapy 5 days a week for 7 weeks.
  • Arm II: Patients receive supplemental oxygen and undergo radiotherapy as in arm I.

Quality of life is assessed at baseline, on days 1 and 16 of radiotherapy, monthly for 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Patients are followed monthly for 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 659 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed locally advanced, unresectable non-small cell lung cancer of 1 of the following subtypes:

  • Adenocarcinoma
  • Squamous cell carcinoma
  • Large cell carcinoma
  • Poorly differentiated carcinoma

• Stage IIIA or IIIB

  • T1 or T2, N2
  • T3, N1 or N2
  • T4, any N
  • Any T, N3
• Histological or cytological confirmation of at least 1 positive lymph node required if the largest mediastinal node that is the basis of stage III disease is less than 2.0 cm in diameter
• Clinically or radiologically measurable disease of at least 2.0 cm
• Partially resected stage IIIB disease allowed provided a measurable lesion remains
• No pleural effusion that is bloody, cytologically positive, or re-accumulated after thoracentesis
• No metastatic disease by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin at least 10 g/dL
• WBC at least 3,000/mm^3
• Absolute granulocyte count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No clinically active congestive heart failure
• No unstable angina
• No severe arrhythmia by ECG

Pulmonary

• FVC and FEV_1 at least 50% of normal
• Resting oxygen saturation by pulse oximetry (SpO_2) at least 90% on room air
• Exercise SpO_2 at least 90% on room air

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile female patients must use effective contraception during and for 30 days after study therapy
• Male patients must use effective contraception during and for 90 days after study therapy
• No loss of more than 10% of body weight within the past 3 months
• No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No significantly altered mental status or dementia that would preclude giving informed consent
• No active infection
• No other serious underlying medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 28 days since prior biologic therapy
• No concurrent colony-stimulating factors (randomized phase only)
• No biologic therapy during and for 1 month after study therapy
• No immune response modifiers during and for 1 month after study therapy

Chemotherapy

• No prior systemic chemotherapy

Endocrine therapy

• No hormonal therapy during and for 1 month after study therapy

Radiotherapy

• No prior thoracic radiotherapy

Surgery

• See Disease Characteristics
• No prior total surgical resection

Other

• More than 28 days since prior investigational drugs or devices
• No prior efaproxiral
• No other cytotoxic therapy during and for 1 month after study therapy