Inclusion Criteria:

- Patients must have a pathologically confirmed diagnosis either at MSKCC or at the
participating site of malignant pleural mesothelioma.

- No evidence of metastatic disease.

- 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 45 mL/min (Creatinine
clearance must be calculated using Cockcroft & Gault method) In cases of concern
about renal toxicity from IMRT, an optional nuclear medicine kidney function scan may
be performed prior to radiation therapy to determine the functional contribution of
each kidney.

- 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.

- No acute congestive heart failure