Inclusion Criteria:

1. Chemotherapy-naive patients with histologically or cytologically confirmed
adenocarcinoma and large-cell carcinoma, classified as stage IIIB not amenable to
curative treatment or stage IV

2. With at least one unidimensionally measurable lesion according to the Response
Evaluation Criteria in Solid Tumors;

3. with an Eastern CooperativeOncology Group performance status of 0 or 1,

4. At least 18 years of age

5. adequate bone marrow reserve and organ function including calculated creatinine
clearance 45 mL/min based on the standard Cockcroft and Gault formula.

6. Prior radiation therapy was permitted if it was completed at least 4 weeks before
study treatment

7. patients had fully recovered from its acute effects.

Exclusion Criteria:

1. peripheral neuropathy > National Cancer Institute Common Toxicity Criteria grade 1

2. progressive brain metastases,

3. uncontrolled third-space fluid retention before study entry.

4. Patients unable to interrupt aspirin and other nonsteroidal anti-inflammatory drugs
or if they were unable or unwilling to take folic acid, vitamin B12, or
corticosteroids.