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Currently, combination systemic chemotherapy is considered as the first-line treatment for patients with metastatic (Stage IV) bladder cancer. The chemotherapeutic regimen that has been used most commonly since 1990 for metastatic bladder cancer is M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin). The median survival rate for patients with metastatic bladder cancer who are treated with M-VAC is only about one-year, however, a small percentage of patients achieve longer survival.

Because of the considerable toxic side-effects of M-VAC, particularly in elderly patients and patients with impaired renal (kidney) function, the search for alternative systemic chemotherapy regimens has been accelerated in recent years. The results of a clinical trial published in 2000 in the Journal of Clinical Oncology (Volume 17; pages 3068-3077) suggested that the combination of gemcitabine and cisplatin (GC) was less toxic than M-VAC with comparable survival rates for patients with advanced and metastatic bladder cancer. Many doctors now consider GC as an alternative standard regimen to M-VAC for patients with advanced and metastatic bladder cancer.

Another chemotherapeutic agent that has recently emerged as a potentially effective second-line treatment for patients with metastatic bladder cancer refractory to cisplatin-based chemotherapy is paclitaxel. Cisplatin is metabolized in the kidneys and, therefore, poses significant risks for patients with impaired kidney function. Paclitaxel, on the other hand, is metabolized in the liver and is, therefore, an alternative to cisplatin for these patients. Although encouraging results have been reported in several clinical trials evaluating combination systemic chemotherapy with paclitaxel-containing regimens, additional studies are required to confirm the efficacy of the taxanes (e.g., paclitaxel, docetaxel) as front-line systemic therapy in patients with metastatic bladder cancer.

Carboplatin, a cisplatin-like agent, produces less renal toxicity, and is commonly used for those patients with impaired renal function who cannot receive cisplatin.