The purposes of this study are: To determine the maximum tolerated dose of Gemcitabine and Platinol followed by Pemetrexed and Gemcitabine in patients with advanced or metastatic transitional cell carcinoma of the urothelium; To determine the safety of Gemcitabine and Platinol followed by Pemetrexed and Gemcitabine and any side effects that might be associated with the combination of these drugs; To determine whether Gemcitabine and Platinol followed by Pemetrexed and Gemcitabine can help patients with advanced bladder cancer live longer; To determine whether Gemcitabine and Platinol followed by Pemetrexed and Gemcitabine can make your tumor smaller or disappear, and for how long.

Inclusion Criteria:

• Biopsy-proven metastatic bladder cancer
• No prior chemotherapy for metastatic disease except before or after surgery, which was completed 6 months before enrollment
• Prior radiation allowed, if it is not the only site of measurable disease and if completed 3 weeks before enrollment
• 18 years of age and older

Exclusion Criteria:

• Pure adeno- or squamous urothelial cancer
• Brain metastases that causes symptoms
• Have not received treatment within the last 30 days with a drug that has not received regulatory approval for any indication
• Inability to take dexamethasone, folic acid or vitamin B12, according to the protocol
• Clinically relevant fluid collection in the lungs or abdomen that cannot be controlled