Purpose of review: This review focuses on chemotherapy in the management of patients with advanced urothelial cancer, with a look towards the future and the next generation of clinical trials.
Recent findings: The recognition that the maximum benefit from conventional combination chemotherapy has been achieved has led to recent initiation of clinical trials evaluating novel agents, targeted agents and the possibility of customizing chemotherapy on the basis of the chemosensitivity.
Summary: Randomized trials have demonstrated that cisplatin-based combination chemotherapy can be considered the standard treatment for fit patients with metastatic urothelial cancer. However, several newer regimens have failed to demonstrate superiority in terms of overall survival when compared to classic methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC). The addition of a third agent to doublet combinations is still uncertain. New drugs including pemetrexed and vinflunine are now being studied for second-line therapy. Progress in the understanding of the molecular biology of bladder cancer and identification of new targeted therapies will provide new opportunities. In addition to newer drug combinations, tailoring of chemotherapy on the basis of molecular characteristics to predict chemosensitivity will provide new challenges.