Pemetrexed Plus Gemcitabine in Renal Cell Cancer

Inclusion Criteria:

* Patients must have histologically or cytologically confirmed advanced non-clear cell RCC. Patients with locally recurrent disease are eligible. Patients with locally advanced unresectable RCC should have measurable metastatic disease to be eligible for the protocol. Patients with bilateral renal cancer are eligible as long as both cancers are of non-clear cell type and patients have metastatic disease.
* Patients must have measurable disease.
* Patients with previously treated or untreated, non-threatening brain metastasis are eligible. For previously treated patients, prior whole brain radiation therapy or stereotactic radiosurgery must be \> 3 months from initiation of current therapy and there can be no plans for concurrent radiation while on this study. Patients who had surgical resection for brain metastasis are eligible to enroll after they recover from surgery.
* Life expectancy \> 8 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Patients must have adequate organ and marrow function as defined below: (1) Hemoglobin \>/= 9g/dl; (2) absolute neutrophil count \>/= 1,500/microL; (3) platelets \>/=100,000/microL; (4) total bilirubin \</= 1.5 mg/dl; (5) aspartate aminotransferase (AST or SGOT) and/or alanine aminotransferase (ALT or SGPT) (SGPT) \</= 2.5 \* institutional upper limits of normal (uln), or \</= 5 \* uln if liver metastasis exists; (6) creatinine clearance (calculated by the Cockcroft-Gault formula) \>/= 45 mL/min
* Patients must have recovered from any effects of surgery and/or radiation therapy and be free of significant detectable infection.
* Female patients of childbearing potential must have a normal plasma beta human chorionic gonadotropin (bHCG) within 24 hours prior to enrolling in the study. Patients with an elevated bHCG will undergo appropriate evaluation to rule out pregnancy (ie referral to OB-Gyn service, ultrasound) and if pregnancy is ruled out and elevated bHCG is determined to be of tumor origin, patients will be permitted to proceed on study.
* Patients of child fathering or childbearing potential must agree to practice a form of medically acceptable birth control while on study
* Patients must give written consent prior to initiation of therapy, in keeping with the policies of the institution. Patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy. The only approved consent is attached to this protocol.

Exclusion Criteria:

* Pregnant or lactating women.
* No prior malignancy is allowed, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 2 years.
* Patients must not have received more than 2 prior systemic therapies for RCC, but patients should not have received any prior chemotherapy for RCC. Chemotherapy given for other types of cancer more than 2 years prior to enrollment on this protocol is permitted.
* Patients must not be scheduled to receive any experimental drug for MRCC while on study. Patients are permitted to be on concomitant bisphosphonates or megestrol acetate. Patients are permitted to receive hematopoietic growth factors according to American Society of Clinical Oncology (ASCO) guidelines.
* Patients must not have had prior radiotherapy to areas of measurable disease, unless they have clearly progressive disease in this site, or there is measurable disease outside the area of prior radiation. Radiotherapy, if needed for palliation, must have been completed prior to enrollment on this study.
* Patients must not have any significant medical disease (other than the malignancy) that, in the opinion of the investigator, would significantly increase the risk for participation in this trial. Examples of exclusion: unstable angina pectoris, New York Heart Association (NYHA) Grade II or greater congestive heart failure, unstable symptomatic cardiac arrhythmias requiring medication (subjects with controlled chronic atrial fibrillation are eligible), myocardial infarction within the last 6 months, uncontrolled hypertension (blood pressure \>160/110 on therapy) or uncontrolled diabetes mellitus.
* Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
* Patients unwilling to participate or unable to comply with the protocol for the duration of the study.
* Inability or unwillingness to take corticosteroid, folic acid or vitamin B12 supplementation.
* Inability to interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5 day period (for short acting NSAIDs) or 8-day period (for long-lasting NSAIDs, such as piroxicam)