The present and future of combination chemotherapy in bladder cancer

The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) has dominated the landscape of chemotherapy for advanced bladder cancer for over 15 years. Randomized studies have shown its superiority over cisplatin alone or in combination with cyclophosphamide and doxorubicin. However, it exhibits a significant toxicity profile and achieves only a slight impact on overall survival. Gemcitabine is among the new cytotoxic drugs in development for treatment of advanced urothelial cancer. The combination of gemcitabine and cisplatin represents a new standard alternative of treatment in the disease based on similar efficacy to and lower toxicity than the classic MVAC regimen. Future drug development will focus on the clinical usefulness of three-drug regimens (including gemcitabine, paclitaxel or docetaxel, and a platinum salt), and nonplatinum-based combinations, as well as showing the impact of adjuvant postcystectomy chemotherapy on survival.