Mesothelioma Clinical Trials Study of Decitabine in Preventing Tumor Growth This study is currently recruiting patients. Sponsored by For more information:National Cancer Institute (NCI)   In preclinical studies, we have demonstrated induction of tumor antigen and tumor suppressor gene expression in lung and esophageal cancer cells as well as malignant pleural mesothelioma cells following DNA hypomethylation using decitabine concentrations which are potentially achievable in clinical settings. In order to assess the feasibility of DNA hypomethylation in solid tumors, patients with inoperable thoracic malignancies will receive two cycles of 72-hour intravenous infusion of decitabine using a phase I study design. Pharmacokinetics, systemic toxicity, and response to therapy will be recorded. Tumor biopsies will be obtained prior to, and after therapy to determine if expression of the NY-ESO-1 cancer testis antigen can be induced by demethylation mechanisms in vivo. Additional analysis will be undertaken to determine if immune recognition of this tumor antigen can be demonstrated following decitabine treatment. Furthermore, because approximately 40% of lung cancers exhibit inactivation of the Rb/CDKN2 pathway by hypermethylation, additional experiments will be undertaken to evaluate the pharmacokinetics for induction of this tumor suppressor pathway in vivo. Results of these studies may enable evaluation of additional agents which are known to facilitate transcription by demethylation or chromatin remodeling mechanisms. Condition Treatment or Intervention Esophageal Cancer Lung Neoplasm Mesothelioma  Drug: Decitabine This is a Phase I test In Phase I clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.    Study Type: Interventional Study Design: Treatment, Safety  Official Title: Phase I Study of Decitabine Mediated Induction of Tumor Antigen and Tumor Suppressor Gene Expression in Patients with Cancers Involving the Lung, Esophagus, or Pleura Further Study Details:  In preclinical studies, we have demonstrated induction of tumor antigen and tumor suppressor gene expression in lung and esophageal cancer cells as well as malignant pleural mesothelioma cells following DNA hypomethylation using decitabine concentrations which are potentially achievable in clinical settings. In order to assess the feasibility of DNA hypomethylation in solid tumors, patients with inoperable thoracic malignancies will receive two cycles of 72-hour intravenous infusion of Decitabine using a phase I study design. Patients will be stratified into two groups: patients who have received 3 or more different prior therapy regimens and patients who have received 2 or less prior therapy treatment regimens. Pharmacokinetics, systemic toxicity, and response to therapy will be recorded. Tumor biopsies will be obtained prior to, and after therapy to determine if expression of the NY-ESO-1 cancer testis antigen can be induced by demethylation mechanisms in vivo. Additional analysis will be undertaken to determine if immune recognition of this tumor antigen can be demonstrated following decitabine treatment. Furthermore, because approximately 40% of lung cancers exhibit inactivation of the Rb/CDKN2 pathway by hypermethylation, additional experiments will be undertaken to evaluate the pharmacokinetics for induction of this tumor suppressor pathway in vivo. Results of these studies may enable evaluation of additional agents which are known to facilitate transcription by demethylation or chromatin remodeling mechanisms. Genders Eligible for Study:  Both Criteria INCLUSION CRITERIA: Patients with histologically or cytologically proven primary small cell, and non-small cell lung cancers, esophageal cancer or pleural mesothelioma, as well as individuals with pleural effusions secondary to extrathoracic malignancies are eligible for evaluation. Patients with extrathoracic metastatic disease are eligible for study provided no intracranial or leptomeningeal metastases are evident. Patients must have had no chemotherapy, biologic therapy, or radiation therapy for their malignancy within 30 days prior to decitabine 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 patient 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 pCO(2) less than 50 mm Hg and pO(2) 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 during childhood and adolescent development. Patients must have a platelet count greater than 100,000, a Hgb greater than 10 gm/dl, a WBC greater than 3500/microliter, 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 60 ml/min. Patients with a history of coronary artery disease, previous transmural myocardial infarction, or congestive heart failure will have cardiology consultation. Subsequent evaluation will consist of stress/redistribution thallium, MUGA scan, or coronary angiography as indicated. Patients with fixed defects on thallium scanning and adequate (greater than 40%) ejection fraction will be eligible following cardiology clearance. 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 NY-ESO-1 and p16 expression prior to, and after, decitabine treatment. EXCLUSION CRITERIA: Patients with primary and metastatic lung or esophageal cancer or malignant pleural mesotheliomas which cannot be readily biopsied by endoscopic or percutaneous fine needle aspiration techniques will be excluded. Patients with limited stage SCLC or operable NSCLC will be excluded. Patients with active intracranial and leptomeningeal metastases will be excluded. Patients who have received resection or radiation therapy for intracranial metastatic disease may be eligible provided there is no evidence of active disease on two MRI scans one month apart and they require no anticonvulsant medications or steroids to control residual symptoms. Patients with life expectancy less than six months will be excluded. Patients with prior decitabine exposure will be excluded. Patients with unstable angina, recent pulmonary embolism, or deep venous thrombosis requiring anticoagulation will be excluded. Pregnant patients and or lactating mothers will be excluded due to the unknown, potentially harmful effects of demethylating agents on fetal and early childhood development. Patients with active infections will be excluded. Patients with HIV will be excluded due to the potential risk of opportunistic infection during decitabine-induced myelosuppression.