• To establish the maximally tolerated dose (MTD) of intraoperative Intrathoracic/Intraperitoneal hyperthermic gemcitabine and cisplatin combination modulated by amifostine and sodium thiosulfate in patients with malignant pleural mesothelioma. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  

• To determine and quantitate the safety of this combination in these patients by defining the dose limiting toxicity. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  
• To study the pharmacokinetics of gemcitabine and cisplatin combination administered in this way. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  

Procedure: Extrapleural pneumonectomy (EPP)
Resection of the lung, the lining of the lung (pleura), the covering of the heart (pericardium), and the muscle that separates the chest and abdomen (diaphragm)
Drug: cisplatin
Given after the tumor is removed as a bath (perfusion) for one-hour
Drug: gemcitabine
Given after the tumor is removed as a bath (perfusion) for one-hour
Drug: amifostine
Given intravenously before perfusion chemotherapy and then 2 hours after the first dose
Drug: sodium thiosulfate
Given intravenously immediately at the end of perfusion chemotherapy

• This is a dose escalation study of gemcitabine with a fixed dose of cisplatin
• Patients will undergo surgery with Extrapleural Pneumonectomy, which entails the removal of the inner and outer lining of the lung (pleura) and the lung itself, including the lining overlying the pericardium and diaphragm. Resection of the pericardium and diaphragm are occasionally necessary to remove all visable tumor. This surgery is part of standard care for malignant pleural mesothelioma.
• After surgery, a one hour lavage with heated cisplatin and or gemcitabine will be administered to the hemithorax (and abdominal regions if the diaphragm is no longer present).
• Patients will remain hospitalized until they have recovered from surgery (usually 7-14 days).
• Patients will return to the hospital during the first month after their surgery to be evaluated by the medical staff.
• Dose escalation: 1) Three patients will be treated at the first dose level of gemcitabine. Labs will be monitored on a weekly basis, including a CBC, Chem-7, and LFT's. In the absence of developing dose-limiting toxicity (DLT) among the first 3 patients treated, dosages can be escalated. DLT will be defined as any grade 3 or higher renal toxicity, thrombocytopenia or other grade 3 toxicity not related to surgery 2) If none of these 3 patients have any toxicity, we will proceed to the next level of gemcitabine. 3) If DLT occurs in 1 of 3 patients at a given dose level, then 3 additional patients are added at that dose (for a total of 6 at this level)If no DLT occurs, we will proceed to the next level of gemcitabine. If DLT occurs in another patient, this dose is considered the maximum tolerated dose (MTD). 4) At any dose, 3 cases of DLT lead to discontinuation of recruitment at that dose and enrollment of 3 additional patients at a lower dose.

Inclusion Criteria:

• Histologically-proven diagnosis of stages I to III malignant mesothelioma of the pleura and negative mediastinal N2 lymph nodes (Malignancy is confined to the affected hemithorax)
• Adequate organ function including the following: adequate cardiac function, pulmonary function, renal and hepatic function and bone marrow reserve
• Adequate overall physical activity
• Surgical candidate for Extrapleural Pneumonectomy (EPP)

Exclusion Criteria:

• Extended disease outside the ipsilateral hemithorax as proven histologically, radiologically and/or intraoperatively
• Have received chemotherapy and or radiation therapy within the last 3 years at the time of study entry
• Serious concomitant systemic disorders
• Second active primary malignancy (to exclude non- melanoma skin cancer)
• Pregnancy at the time of the operation
• Psychiatric or addictive disorder which would preclude obtaining informed consent