Optimizing therapeutic strategies in advanced bladder cancer: update on chemotherapy and the role of targeted agents.

M-VAC (cisplatin, methotrexate, adriamycin, vinblastine) combination chemotherapy has been the standard of care in fit patient with advanced urothelial tumors for long time. Phase III trials have evaluated new combinations such as gemcitabine/cisplatin, carboplatin/paclitaxel, docetaxel/cisplatin and interferon-alpha/5-fluorouracil/cisplatin. Even though these new regimens have failed to demonstrate superiority in terms of overall survival when compared to the classical M-VAC, the combination of gemcitabine/cisplatin has proved to be a new standard alternative showing more favorable toxicity profile and similar efficacy. Along the same line, the addition of a third agent (TCG) has been studied in a large phase III EORTC trial. This study shows a trend in favor of the triplet and suggests different patterns of chemosensitivity favoring primary bladder carcinoma. In addition to the new active drug combinations the role of targeted agents as monotherapy, in combination with chemotherapy or as maintenance post-chemotherapy is currently under study. Finally, chemotherapy optimization using clinical and molecular markers predicting chemosensitivity and prognosis are emerging.