S9900: Surgery With or Without Combination Chemotherapy in Treating Patients With Non-small Cell Lung Cancer

OBJECTIVES:

• Compare survival of patients with previously untreated stage IB, II, or selected IIIA non-small cell lung cancer after preoperative chemotherapy comprising paclitaxel and carboplatin plus surgery vs surgery alone.
• Compare these regimens in terms of operative mortality and other toxic effects in these patients.
• Evaluate the response rates (confirmed and unconfirmed) and toxic effects associated with combined paclitaxel and carboplatin in these patients.
• Obtain samples for correlation of radiologic, pathologic, molecular, and biologic factors with the outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinical stage (IB or IIA vs IIB or IIIA).

Patients are randomized to one of two treatment arms:

• Arm I: Patients undergo thoracotomy. All accessible hilar (level 10) lymph nodes are dissected, and complete mediastinal lymph node sampling is performed.
• Arm II: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for a maximum of 3 courses in the absence of disease progression or unacceptable toxicity. Within 2-6 weeks of course 3, patients undergo thoracotomy and lymph node dissection as in arm I.

Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually until year 10.

PROJECTED ACCRUAL: A total of 600 patients (300 per treatment arm) will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven non-small cell lung cancer (NSCLC), meeting 1 of the following staging criteria:

• Stage IB (T2, N0)
• Stage II

• T1-2, N1 with negative mediastinoscopy OR
• T3, N0
• Selected stage IIIA with negative mediastinoscopies

• T3, N1, excluding superior sulcus
• Positive level 10 hilar nodes allowed if mediastinoscopy negative
• Apical tumors with no clinical symptoms allowed
• No symptomatic tumors (T3, N0 or T3, N1) involving the superior sulcus

• No Pancoast's tumors
• Negative mediastinoscopy required in all patients with clinically positive mediastinal or hilar lymph nodes to ensure no N2 disease
• Bidimensionally measurable or evaluable disease by chest x-ray or contrast-enhanced CT scan

• T3, N0 disease assessable only by bronchoscopy must be affirmed by 2 observers and documented by photograph that includes main carina

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0 or 1

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• WBC at least 4,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT or SGPT no greater than 2 times ULN
• Alkaline phosphatase no greater than 2 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN
• Creatinine clearance at least 50 mL/min

Pulmonary:

• See Disease Characteristics
• Preresection FEV_1 greater than 2.0 L OR
• Predicted postresection FEV_1 greater than 1.0 L
• No postobstructive pneumonia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious infection
• No other serious medical condition that would preclude study compliance
• No prior allergic reactions to drugs containing Cremophor
• No prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy for NSCLC
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior systemic radiotherapy for NSCLC
• No concurrent radiotherapy

Surgery:

• At least 5 years since prior resection of lung disease

Other:

• No other concurrent investigational therapy
• No other concurrent anticancer therapy