Study Using Chemotherapy +/- Pleurectomy/Decortication Followed By Intensity Modulated Radiation Therapy

To determine the safety (specifically in regards to pneumonitis) of chemotherapy +/- pleurectomy/decortication followed by IMRT to the pleura in patients with malignant pleural mesothelioma [ Time Frame: conclusion of study ] [ Designated as safety issue: Yes ]

To determine the response rate, progression free and overall survival rates of patients with malignant pleural mesothelioma treated with chemotherapy, with or without P/D, followed by IMRT to the pleura. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]
To determine the relationship between response to treatment and the levels of soluble mesothelin-related peptide (SMRP) and osteopontin. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]
To determine the pattern of progression: local recurrence versus metastatic disease. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]

Inclusion Criteria

Patients must have a pathologically confirmed diagnosis of malignant pleural mesothelioma.
No prior chemotherapy for mesothelioma.
No prior radiation therapy except for localized prostate or pelvic radiation
Patient age ≥ or = to 18 years on day of signing informed consent.
Karnofsky performance status ≥ or = to 70%
Patients must have the ability to take folic acid, Vitamin B12, and dexamethasone according to protocol.
Patient must have the ability to interrupt NSAIDS 2 days before (5 days for longacting NSAIDs), the day of, and 2 days following administration of pemetrexed.
Pulmonary Function Tests:
FEV1 ≥ 30% of predicted postoperative (ppoFEV1) (as if the patient underwent a pneumonectomy) based on the following formula using the quantitative V/Q scan:
Predicted post-resection FEV1 = FEV1 x % perfusion to uninvolved lung from the quantitative V/Q scan report.
DLCO > 35% predicted
Patient must have adequate organ function as indicated by the following laboratory values:
Hematological:
Absolute neutrophil count ≥ or = to 1,500 /mcL
Platelets ≥ or = to 100,000 / mcL
Renal Calculated creatinine clearance (CrCl) ≥ or = to 55 mL/min (Creatinine clearance must be calculated using Cockcroft & Gault method)
Hepatic
Serum total bilirubin ≤ or = to 1.5 X upper limit of normal (ULN) AST (SGOT) or ALT (SGPT) ≤ or = to 3.0 X ULN

Exclusion Criteria

Pregnant or lactating women, or men or women not using effective contraception.
Patients with resectable disease for whom extrapleural pneumonectomy is necessary.
Patients with an active infection that require systemic antibiotics, antiviral, or antifungal treatments.
Patients with a concurrent active malignancy.
Patients with serious unstable medical illness.
Presence of third space fluid that cannot be controlled by drainage. For patients who develop or have baseline clinically significant pleural effusions before or during initiation of pemetrexed therapy consideration should be given to draining the effusion prior to dosing.

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