low accrual due to competing study for same group of patients

Despite the best surgical efforts, complete removal of mesothelioma is possible in approximately 30% of the patients. When surgical removal is complete, chemotherapy followed by radiation therapy is recommended as an effort to improve control over the cancer and survival. This combination of treatments is called TRIMODALITY therapy. Unfortunately, the chances for the tumor coming back after TRIMODALITY therapy remains high. When surgical removal is not complete or not possible, some patients may receive chemo and/or radiation therapy to achieve control over the cancer, but the chances of tumor to growth again remains high and the chances of long term survival remains low.

The combination of Pemetrexed (Alimta) with Cisplatin has been approved as one of the standard chemotherapy drug combinations for the treatment in advanced Malignant Pleural Mesothelioma, and there is likely a group of patients who may benefit and potentially be cured by this therapy. In an effort to achieve a better chance of complete removal of the cancer and long term survival, the investigators are interested in using this drug combination of Pemetrexed + Cisplatin before surgery and offer radiation therapy after surgery.

Inclusion Criteria:

1. Histologically proven diagnosis of MPM stages I to III. Patients will be clinically staged using the AJCC/UICC TNM staging criteria (see Protocol Appendix 2). Eligible stages:

   • Patients must be M0.
   • Patients with T1, T2, and T3 disease (without cardiac involvement) are eligible. T status can be established clinically and radiologically or at exploratory thoracotomy without surgical resection.
   • Patients with N0, N1, or N2 disease are eligible.

2. Performance status of 0 to 2 on the ECOG performance status schedule. See protocol Appendix 3

3. No prior systemic chemotherapy. No prior intracavitary cytotoxic drugs or immunomodulators, unless given for the purpose of chemical pleurodesis.

4. No previous surgical procedure for mesothelioma, with the exception of previous chemical pleurodesis and biopsy.

5. No previous radiation therapy for mesothelioma, or to the thorax.

6. Patients must be judged to be suitable candidates for this therapy at the UHN by the attending medical oncologist, thoracic surgeon, and radiation oncologist before enrolment.

7. Estimated life expectancy of at least 12 weeks.

8. Adequate organ function including the following:

   • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ³1,500/uL , platelets ³100,000/uL, hemoglobin ³ 9g/dL
   • Hepatic: bilirubin £1.5 times institutional upper limit of normal, alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) £3 times institutional upper limit of normal
   • Renal: Creatinine £1.5 times institutional upper limit of normal; or Creatinine clearance ³50 mL/min/1.73 m² for patients with creatinine levels above institutional normal upper limit level. Cockcrot and Gault formula Appendix 4.
   • Pulmonary function tests:

   Predicted post-operative DLCO (ppoDLCO) of > 35%.

   If the ppoDLCO is \