Study of Weekly Paclitaxel, Carboplatin and Irinotecan to Treat Lung Cancer

Inclusion Criteria:

* Histological or cytological diagnosis of non-small cell lung cancer.
* Malignant pleural effusion proven by cytological examination.
* Patient must have stage IIIB or IV disease with malignant pleural effusion.
* We plan to recruit 16 patients who have smoked cigarettes of at least 20 pack per year, 16 patients who do not smoke but have been exposed to second hand smoking by living with a person who has smoked 20 pack per year cigarette in the same household and 16 patients who are non-smokers (never smoked) and no second hand smoking exposure in the same household. The accrual will be stopped once the number of patients is reached in each group.
* ECOG PS 0, 1 or 2.
* Measurable disease (in addition to malignant pleural effusion).
* No prior chemotherapy for metastatic or recurrent disease. Patient may have surgery or radiation or combined chemoradiation, or neoadjuvant chemotherapy at primary diagnosis. This kind of chemotherapy will not be counted as patient has had prior chemotherapy for metastatic or recurrent NSCLC.
* WBC \> 3500/uL and ANC \> 2,000/uL, platelet \> 100,000/uL AST/ALT \< 3 X UNL, bilirubin \< 1.5 mg/dL ( or \< 35 uM), creatinine \< 1.5 mg/dL (or \< 125uM for men and 90uM for women).
* Age \> 18
* No history of congestive heart failure, myocardial infarction or life-threatening arrhythmia (such as ventricular tachycardia, supraventricular tachycardia, brachycardia \< 40/min or atrial fibrillation or flutter with ventricular rate \> 150/min) within 6 months of entry.
* Signed informed consent
* Negative mammogram and ovaries examination by CT scans and no history of breast cancer or ovarian cancer in female patients.
* Negative pregnancy test in female menstruating patient within one week of starting chemotherapy and use of effective contraceptive methods during study.
* Patients with brain metastasis will be eligible provided their neurological abnormality is stable or improved after whole brain radiation, stereostatic radiosurgery or gamma knife treatment and/or dexamethasone for 3 weeks and patients fulfil all other eligibility criteria.

Exclusion Criteria:

* ECOG performance status 3 or worse.
* Any prior chemotherapy regimen for metastatic or recurrent diseases.
* No measurable disease, even after drainage of pleural effusion.
* ANC \< 1,999/uL or Bilirubin \> 1.5 mg/dL (or \> 35uM)
* Plt \< 100,000/uL or
* ALT/AST \> 3 x UNL
* Creatinine \> 1.5mg/dL (or \> 125uM)

Patient has history of congestive heart failure, myocardial infarction or life-threatening arrhythmia (such as ventricular tachycardia, supraventricular tachycardia, atrial fibrillation/flutter with ventricular rate \> 150/min or bradycardia \< 40/min) within 6 months before entry.

Prior history of breast cancer or ovarian cancer in female patients or any cancer except cured cervical carcinoma in-situ or skin cancer.

Fasting blood sugar \> 200 mg/dL (\> 14uM) except in patients on dexamethasone for brain metastases.