Based on results from earlier clinical trials, Pemetrexed may have antitumor activity as a first-line agent in the treatment of mesothelioma. Given this, it is hypothesized that Pemetrexed may be active in second-line mesothelioma in which the standard treatment is best supportive care. This study will compare survival of previously treated patients with malignant pleural mesothelioma who receive Pemetrexed plus best supportive care to the survival of similar patients who receive best supportive care alone.

Inclusion Criteria:

• Histologically proven diagnosis of mesothelioma of the pleura.
• received only one prior systemic chemotherapy regimen for advanced or metastatic disease
• Performance status of 70 or higher on the Karnofsky Performance Status Scale
• Males or females at least 18 years of age
• Adequate organ function

Exclusion Criteria:

• Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy
• Pregnancy or breastfeeding
• Brain metastasis
• Prior treatment with Pemetrexed
• Inability or unwillingness to take folic acid or vitamin B12 supplementation