The intent of this protocol is to screen a new agent for activity in patients with advanced or recurrent endometrial carcinoma. This phase II trial is studying how well pemetrexed disodium works in treating patients with advanced or recurrent endometrial carcinoma.

Inclusion Criteria:

• Patients must have recurrent or persistent endometrial adenocarcinoma, which is refractory to curative therapy or established treatments.
• Patients must have measurable disease.
• Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma.
• Patients must have signed an approved informed consent.
• Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception during the study and for at least 3 months following the last dose of Pemetrexed.
• Patients must discontinue nonsteroidal anti-inflammatory (NSAIDs) medications 2-5 days prior to and for 1-2 days after receiving Pemetrexed, depending on the half-life of the NSAIDs treatment.
• Patients must agree to this schedule in conjunction with every dose of Pemetrexed.
• Patients must receive 350-1000 mcg of folic acid (e.g. one prenatal vitamin) starting 7 days prior to the first treatment with Pemetrexed.
• Patients must be able to ingest 350-1000 mcg of folic acid daily until 3 weeks after the last dose of Pemetrexed.
• Patients must receive 4 mg Dexamethasone by mouth twice daily, 1 day prior to the dose, the day of and the day after every dose of Pemetrexed.
• Patients must receive a 1000 mcg vitamin B12 injection 7 days prior to receiving the first treatment with Pemetrexed.
• Patients must agree to receive 1000 mcg vitamin B12 injection every 9 weeks until 3 weeks after the last dose of Pemetrexed.

Exclusion Criteria:

• Patients who have had prior therapy with Pemetrexed
• Patients who have received radiation to more than 25% of marrow bearing areas