A Phase II Study of Pemetrexed and Carboplatin in the Treatment of Esophageal Cancer

Inclusion Criteria: * Patients must have a histologically or cytologically proven metastatic or recurrent esophageal cancer. Both adenocarcinoma and squamous carcinoma are eligible for the study. Patients with small cell carcinoma or sarcoma of the esophagus are not eligible for the study. * Patients may have had no prior chemotherapy treatment for metastatic esophageal cancer. Patients may have had chemotherapy with 5-FU combined with definitive radiotherapy for curative intent in the adjuvant, neoadjuvant, or definite setting for locally advanced esophageal cancer, if no less than one year prior to trial enrollment. Patients may not have received pemetrexed in the past. * Patients who have had radiotherapy for esophageal cancer must have completed radiotherapy at least four weeks prior to entry in the study. * Patients need to have measurable disease. * Lesions that are not considered measurable include the following: * Bone lesions * Brain metastases or leptomeningeal disease * Ascites * Pleural/pericardial effusion * Abdominal masses that are not confirmed and followed by imaging techniques * Cystic lesions * Tumor lesions situated in a previously irradiated area * ECOG) performance status of 0-2. * Life expectancy of \>=12 weeks. * Patients must have adequate bone marrow function defined as: white blood cells (WBC) \>= 3000/mm\^3, absolute neutrophil count (ANC) \>= 1,500/mm\^3, hemoglobin \>= 9.0 g/dL, and platelet count \>= 100,000/mm\^3. * Patients must have adequate liver function defined as: Bilirubin \<= 1.5 x institutional normal and ALT/AST \< 3 x institutional normal. * Patients must have adequate renal function defined as: serum creatinine \<= 3.0 mg/dL and creatinine clearance \>= 45 mL/min. * Radiation therapy for brain metastases should be completed at least four weeks prior to enrollment to this protocol. * Patients must have recovered from uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or uncontrolled symptomatic cardiac arrhythmia. * Patients must be able to be compliant with premedications of dexamethasone, folic acid, and vitamin B12. * For all sexually active women of child-bearing age, the use of adequate contraception (hormonal or barrier method of birth control) will be required prior to study entry and for the duration of study participation. * Age \>= 18 years. * Written consent. * Ibuprofen (400 mg qid) can be administered with Alimta in patients with normal renal function (creatinine clearance \> 80 mL/min Exclusion Criteria: * Patients with third-space fluid (pleural effusions, ascites, etc.) uncontrolled by drainage. * Pregnant or nursing females * Patients who have had pre-existing neuropathy greater than or equal to grade 2. * Patients with known active CNS metastases.