Chemotherapy Plus Radiation Therapy With or Without Surgery in Treating Patients With Stage IIIA Non-small Cell Lung Cancer
Chemotherapy Plus Radiation Therapy With or Without Surgery in Treating Patients With Stage IIIA Non-small Cell Lung Cancer
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor
 cells. It is not yet known if chemotherapy plus radiation therapy is more effective with or
 without surgery for lung cancer.

 PURPOSE: Randomized phase III trial to compare the effectiveness of combining cisplatin,
 etoposide, and radiation therapy with or without surgery in treating patients who have stage
 IIIA non-small cell lung cancer.
OBJECTIVES:

 Primary

 -  Compare the progression-free survival, median (2-year) survival, and long-term (5-year)
 survival in patients with newly diagnosed, stage IIIA (N2) non-small cell lung cancer
 treated with radiotherapy concurrently with cisplatin and etoposide with or without
 surgical resection.

 Secondary

 -  Compare the patterns of local and distant failure in patients treated with these
 regimens.

 -  Determine the relationship of tobacco use, alcohol use, and diet with toxicity of these
 regimens and outcome in both men and women.

 OUTLINE: This is a randomized, multicenter study. Patients are stratified by contralateral
 mediastinal sampling or biopsy (yes vs no), tumor stage (T1 vs T2 vs T3), and performance
 status (70-80% vs 90-100%). Patients are randomized to 1 of 2 treatment arms.

 -  Arm I: Patients receive induction with cisplatin IV over 1 hour on days 1 and 8 and
 etoposide IV over 1 hour on days 1-5. Treatment continues every 4 weeks for 2 courses in
 the absence of disease progression or unacceptable toxicity. Beginning within 24 hours
 of the first dose of chemotherapy, patients undergo induction radiotherapy 5 days a week
 for 5 weeks in the absence of disease progression or unacceptable toxicity. Patients
 without local progression or distant metastases at 2-4 weeks after completion of course
 2 undergo resection approximately 3-5 weeks after completion of course 2. All visible,
 accessible bronchopulmonary, hilar, and mediastinal lymph nodes are excised. The choice
 of surgical procedure (thoracotomy, lobectomy, or pneumonectomy with en bloc resection
 of tumor extending into the parietal pleura, chest wall, pericardium, or diaphragm) is
 at the discretion of the surgeon. Patients who undergo resection receive 2 additional
 courses of chemotherapy alone beginning 4-6 weeks postoperatively. Patients with
 unresectable disease or who are medically unfit for or refuse resection receive 2
 additional courses of chemotherapy alone beginning immediately after completion of
 course 2.

 -  Arm II: Patients undergo induction chemoradiotherapy as in arm I but do not undergo
 resection. Patients without local progression or distant metastases within 1 week before
 anticipated completion of induction radiotherapy receive 2 additional courses of
 chemotherapy beginning immediately after completion of course 2. Patients without local
 or distant progression after completion of course 4 undergo boost radiotherapy for 8
 days.

 Patients are followed every 2 months for 1 year, every 3 months for 2 years, and then every 6
 months thereafter.

 PROJECTED ACCRUAL: A total of 510 patients will be accrued for this study within 4.9 years.
DISEASE CHARACTERISTICS:

 -  Histologically or cytologically proven newly diagnosed, stage IIIA (T1-3, N2)
 non-small cell lung cancer

 -  Eligible subtypes:

 -  Adenocarcinoma

 -  Large cell carcinoma

 -  Squamous cell carcinoma

 -  Nonlobar and nondiffuse bronchoalveolar cell carcinoma

 -  Measurable or evaluable disease on chest x-ray and/or contrast CT scan

 -  Contrast thoracic CT required to complete staging

 -  Single primary bronchogenic tumor (no more than 1 parenchymal lung lesion)

 -  Pleural effusions allowed if 1 of the following conditions is met:

 -  Negative cytology on thoracentesis if effusions present before mediastinoscopy or
 exploratory thoracotomy

 -  Effusion seen on CT scan but not on chest x-ray and deemed too small to tap under
 CT or ultrasound guidance

 -  Positive ipsilateral mediastinal node(s) with or without positive ipsilateral hilar
 nodes

 -  Mediastinal nodes separate from primary lesion on CT scan or surgical exploration

 -  Histologic or cytologic proof of N2 disease by thoracotomy, mediastinoscopy,
 mediastinotomy, Chamberlain procedure, Wang needle, or fine needle aspiration
 under bronchoscopic or CT guidance

 -  Nodal biopsy or aspiration waived if all of the following conditions are met:

 -  Paralyzed left true vocal cord documented by bronchoscopy or indirect
 laryngoscopy

 -  Nodes visible in Level 5 region on CT scan

 -  Distinct primary lesion separate from nodes on CT scan

 -  All mediastinal nodal involvement mapped (positive or negative)

 -  No positive nodes in contralateral mediastinum (supraclavicular areas and higher) and
 neck

 -  Mediastinoscopy, mediastinotomy, Chamberlain procedure, or thoracotomy required
 for nodes larger than 1 cm on contrast CT scan

 -  Surgery waived if nodes negative or no larger than 1 cm on CT scan

 -  Lymphadenopathy allowed if biopsy proof of a benign cause

 -  No metastases by contrast CT or MRI scan of the brain, bone scan, CT scan of the lungs
 to exclude other ipsilateral or contralateral parenchymal lesions, and contrast CT
 scan of the upper abdomen including entire liver and adrenals

 -  No hepatomegaly or splenomegaly by physical examination or CT scan unless
 documentation of a benign cause

 -  No pericardial effusion

 -  No superior vena cava syndrome

 -  No prior diagnosis of lung cancer

 PATIENT CHARACTERISTICS:

 Age:

 -  18 and over

 Performance status:

 -  Karnofsky 90-100% (70-80% allowed if albumin at least 0.85 times lower limit of normal
 and weight loss no greater than 10% within 3 months before diagnosis)

 Hematopoietic:

 -  White blood cell count (WBC) at least 4,000/mm^3 OR

 -  Granulocyte count at least 2,000/mm^3

 -  Platelet count normal

 -  Hemoglobin at least 10.0 g/dL (less than 8.5 g/dL allowed if no marrow involvement
 with tumor)

 Hepatic:

 -  See Performance status

 -  Bilirubin no greater than 1.5 times upper limit of normal (ULN)*

 -  Serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate
 transaminase (SGPT) no greater than 1.5 times ULN* NOTE: * Unless documentation of a
 benign cause

 Renal:

 -  Creatinine clearance at least 50 mL/min

 Cardiovascular:

 -  No myocardial infarction within the past 3 months

 -  No active angina

 -  No unstable arrhythmia

 -  No congestive heart failure

 Pulmonary:

 -  Forced expiratory volume at one second (FEV1) at least 2.0 liters OR

 -  Predicted postresection FEV1 at least 800 mL based on quantitative V/Q scan

 -  Diffusion capacity of lung for carbon monoxide (DLCO) at least 50% predicted
 (corrected for hemoglobin) if pneumonectomy planned or likely after induction
 chemotherapy

 Other:

 -  No clinically significant hearing loss unless willing to accept the potential of
 further loss

 -  No symptomatic peripheral neuropathy

 -  No peptic ulcer disease under active treatment

 -  No other medical illness not controllable by appropriate medical therapy

 -  No other malignancy within the past 5 years except adequately treated basal cell or
 squamous cell skin cancer, carcinoma in situ of the cervix, or ductal or lobular
 carcinoma in situ of the breast

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  No concurrent colony-stimulating factors

 Chemotherapy:

 -  No prior chemotherapy for lung cancer

 -  No concurrent chemotherapy for another condition (such as arthritis)

 Endocrine therapy:

 -  Not specified

 Radiotherapy:

 -  No prior radiotherapy for lung cancer

 Surgery:

 -  See Disease Characteristics

 -  No prior resection of primary tumor