RATIONALE: Determination of genetic changes in patients with non-small cell lung cancer may
help predict the outcome of treatment. Drugs used in chemotherapy use different ways to stop
tumor cells from dividing so they stop growing or die. Combining more than one drug, and
giving them before surgery, may shrink the tumor so that it can be removed during surgery.
PURPOSE: Phase II trial to study genetic changes and the effectiveness of combining
vinorelbine with gemcitabine before surgery in treating patients who have stage IB, stage
II, or stage III non-small cell lung cancer.
- Determine the frequency of expression of epithelial markers CK19, CK20, MUC1, and MUC5
(by reverse transcriptase-polymerase chain reaction) in lymph node tissue and blood
samples of patients with resectable stage IB-III non-small cell lung cancer treated
with neoadjuvant vinorelbine and gemcitabine followed by surgery.
- Determine the expression of the multidrug resistance-associated protein gene before and
after treatment with this regimen in these patients.
- Determine the global expression profile of genes (by microarray technology) in tumor
tissue of patients treated with this regimen.
- Determine the frequency of loss of heterozygosity at several loci on chromosomes 3p,
9p, and 11p before and after treatment with this regimen in these patients.
- Determine the percent positivity of cells that stain for MCM2 and CDC6 (prereplicative
complex) by immunohistochemistry before and after treatment with this regimen in these
- Determine the feasibility of this regimen in these patients.
- Determine the pathological response rates in patients treated with this regimen.
- Determine the side effects of this regimen in these patients.
- Determine the disease-free and overall survival of patients treated with this regimen.
- Determine the autologous immune response in patients treated with this regimen.
OUTLINE: Patients receive vinorelbine IV over 6-10 minutes and gemcitabine IV over 30
minutes on days 1, 8, 22, and 29 in the absence of disease progression or unacceptable
Patients with no disease progression by scans or bronchoscopy undergo surgical resection
between days 57-70 (weeks 8-10).
Loss of heterozygosity (LOH) at loci on chromosomes 3p, 9p, and 11p is assessed in blood
specimens, tumor tissue, and noncancerous tissue before and after chemotherapy. Specimens
are also examined for molecular markers of occult metastasis using reverse
transcriptase-polymerase chain reaction. Multidrug resistance-associated protein gene
expression is also determined using microarray technology.
Patients are followed every 3 months for 2 years, every 6 months for 5 years, and then
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 2 years.
- Histologically confirmed non-small cell carcinoma of the lung
- May be confirmed at the initial bronchoscopy and mediastinoscopy
- Stage IB (T2, N0, M0)
- Stage IIA (T1, N1, M0)
- Stage IIB (T2-3, N0-1, M0)
- Stage IIIA (T1-3, N1-2, M0)
- stage IIIB (2 lesions in 1 lobe [T4])
- No N3 lymph nodes (contralateral mediastinal/hilar and supraclavicular/scaline) OR T4
primary tumor (malignant pleural effusion or mediastinal invasion) by clinical
staging criteria (seen on CT or PET scan and proven by mediastinoscopy)
- No metastatic disease (except N1 or N2 disease) or malignant pleural effusion*
detected on preoperative evaluation
- No exudative effusions (even if cytologically negative)
- Pleural fluid is considered exudative if the following apply:
- Ratio of pleural fluid protein to serum protein is greater than 0.5
- Ratio of pleural fluid lactic dehydrogenase (LDH) to serum LDH is at
- Pleural fluid LDH is greater than 200 IU/L
- No multiple areas of fluorodeoxyglucose (FDG) uptake** outside the area of the
primary tumor in the lung NOTE: *Effusions visible only on CT scan and not large
enough for safe thoracentesis are allowed
NOTE: **If only 1 area shows an increase in FDG uptake, the area of concern requires
further evaluation (e.g., biopsy) to exclude metastatic disease
- Bidimensionally measurable or evaluable disease* NOTE: *Lesions apparent on chest CT
scan (e.g., ill-defined masses associated with post obstructive changes and
mediastinal or hilar adenopathy measurable in 1 dimension) are considered evaluable
- 18 and over
- Not specified
- Not specified
- WBC at least 3,000/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 9 g/dL
- Bilirubin no greater than 1.5 mg/dL
- AST or ALT no greater than 1.5 times upper limit of normal
- Creatinine no greater than 1.5 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Deemed medically fit for surgical resection
- No other active malignancy within the past 2 years except nonmelanoma skin cancer or
carcinoma in situ of the cervix
- No psychological, sociological, or geographical condition that would preclude study
PRIOR CONCURRENT THERAPY:
- Concurrent participation in the RPCI vaccine study (postoperative vaccination with
autologous tumor-associated antigen-pulsed dendritic cells) is allowed
- No prior chemotherapy for lung cancer
- No concurrent participation in another study involving other chemotherapy agents
- Not specified
- No prior radiotherapy for lung cancer
- No concurrent participation in another study involving radiotherapy
- No prior surgery for lung cancer
- More than 3 months since other prior major surgery (e.g., coronary artery bypass
- No other prior therapy for lung cancer
- No other concurrent antineoplastic agents
- Concurrent participation in observational studies requiring bloodwork, radiographs,
pulmonary function tests, or quality of life studies is allowed