Inclusion Criteria

- INCLUSION CRITERIA:

Patients with histologically or cytologically proven primary small cell or non-small cell
lung cancers, advanced esophageal cancer, or pleural mesotheliomas are eligible for
evaluation. In addition, patients with cancers of nonthoracic origin with metastases to
the lungs or pleura are eligible for evaluation.

Patients with intracranial metastases which have been treated by surgery or radiation
therapy may be eligible for study provided there is no evidence of active disease and no
requirement for anticonvulsant therapy or steroids following treatment.

Patients with prior Decitabine or Depsipeptide exposure are eligible for study provided
they have not experienced dose limiting toxicity at the dose of DAC or DP that they are
scheduled to receive.

Patients with prior or current celecoxib exposure are eligible for study provided that it
has been intermittent, or of short term duration (less than 1 month).

Patients must have had no chemotherapy, biologic therapy, celecoxib exposure, or radiation
therapy for their malignancy within 30 days prior to treatment. Patients may have
received localized radiation therapy to non-target lesions provided that the radiotherapy
is completed 14 days prior to commencing therapy, and the patients has recovered from any
toxicity.

Patients must have an ECOG performance status of 0-2.

Patients must have adequate pulmonary reserve evidenced by FEV1 and DLCO greater than the
30% predicted, and pCO2 less than 50 mm Hg and pO2 greater than 60 mm Hg on room air ABG.

Patients must be 18 years of age or older due to the unknown effects of demethylating
agents and HDAC inhibitors during childhood and adolescent development.

Patients must have a platelet count greater than 100, 000, an ANC equal to or greater than
1500 without transfusion or cytokine support, a normal PT, and adequate hepatic function
as evidenced by a total bilirubin of less than 1.5 x upper limits of normal. Serum
creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater
than 70 ml/min/1.73m(2).

All patients will have cardiology consultation. Subsequent evaluation will consist of
stress/redistribution thallium, 24th ambulatory EKG monitoring, ECHO, cardiac MR, or
coronary angiography as indicated.

Patients must be aware of the neoplastic nature of his/her illness, the experimental
nature of the therapy, alternative treatments, potential benefits, and risks. The patient
must be willing to sign an informed consent, and undergo tumor biopsies to evaluate target
gene expression prior to, and after, decitabine/depsipeptide treatment.

EXCLUSION CRITERIA:

Patients with primary and metastatic cancers involving the lungs or pleura which cannot be
readily biopsied by endoscopic or percutaneous fine needle aspiration techniques will be
excluded.

Patients with untreated limited stage SCLC, and operable NSCLC or operable esophageal
cancer will be excluded.

Patients who have received three or more systemic cytotoxic treatment regimens will be
excluded due to possible cumulative marrow suppression.

Patients with active intracranial and leptomeningeal metastases as well as those requiring
anticonvulsant medications will be excluded.

Patients with life expectancy less than three months will be excluded.

Patients with pulmonary embolism, or deep venous thrombosis, or prosthetic heart valves
requiring anticoagulation will be excluded.

Cardiac exclusion criteria, patients with known cardiac abnormalities such as:

-Uncontrolled arrhythmias

History of serious ventricular arrhythmias not controlled by coronary artery bypass
surgery.

Patients with a history of sustained VT, VF, Toursades de Pointes, or cardiac arrest who
do not have an automatic implantable cardioverter defibrillator in place

Congenital Long QT syndrome or QTc greater than 480 msec

Patients with Mobitz II second degree block who do not have a pacemaker

Patients with any cardiac arrhythmia requiring anti-arrhythmic medication other than a
beta blocker or calcium channel blocker

Patients in whom digitalis cannot be discontinued

- Decompensated heart failure (NYHA Class II or IV)

- LVEF less than 50% by MUGA scan or echocardiogram

- Hypertrophic or restrictive cardiomyopathy from prior treatment of other causes and
patients with left ventricular hypertrophy

- Uncontrolled hypertension (i.e greater than or equal to 160/95)

- Myocardial infarction within one year of study

- Clinical significant active myocardial ischemia on the basis of nuclear imaging or
angiography

- History of coronary artery disease (e.g. angina Canadian Class II-Iv or positive
stress imaging study)

- Patients with other cardiac disease may be excluded at the discretion of the PI
following consultation with cardiology

Co-medication causing QTc prolongation unless a 5 half-life washout period has elapsed
between discontinuing the drug and entering this study.

Pregnant patients and lactating mothers will be excluded due to the unknown, potentially
harmful effects of demethylating agents and HDAC inhibitors on fetal and early childhood
development.

Patients with active infections will be excluded.

Patients with HIV infection will be excluded due to the potential risk of opportunistic
infection during DAC/DP-induced myelosuppression and potentially deleterious activation of
viral gene expression.

Patients should not be using hydrochlorothiazide diuretics if entered on this protocol.
Therefore, patients who must use hydrochlorothiazide diuretics will be excluded.