Metastatic Bladder Cancer: Role of Chemotherapy and New Agents

The M-VAC chemotherapy regimen has been widely used in locally advanced as well as in metastatic disease. Since only a proportion of patients with advanced disease will survive, there is a dire need to identify patients who will respond to chemotherapy and to identify new agents, targets and strategies to improve treatment outcome. Approaches to the management of advanced urothelial cancer include: intensifying the dose intensity, doublet and triplet combination chemotherapy, sequential regimens, reducing toxicity in unfit or elderly patients, and the use of biologic targeted therapies and promising new chemotherapeutic agents. These include MTA, the epothilones, topoisomerase inhibitors and vinflunine which act upon folate metabolism or upon different phases of the cell cycle. New agents that are coming into clinical trials include farnesyl transferase inhibitors, several growth factors receptor inhibitors, anti-sense therapy and COX-2 inhibitors. Significant progress has been made in understanding the molecular biology of cancer. Numerous novel agents, many of which are in clinical trials, have been developed to target various processes of tumor progression. The rationale behind application of these molecularly targeted therapies is to overcome resistance to cytotoxic therapies. Bladder cancer represents a unique model for targeted therapy. As our understanding increases, integration of newer biologic agents will condition future trials, and our ability to target bladder and urothelial cancers will be enhanced.