Gemcitabine, paclitaxel, pemetrexed and other newer agents in urothelial and kidney cancers.

Significant progress has been made in understanding the biology of urothelial and kidney cancers. Approaches to advanced urothelial cancer include dose intensification, reducing toxicity in unfit or elderly patients, doublet and triplet combination chemotherapy and sequential regimens. Promising new chemotherapeutic agents such as the epothilones, pemetrexed (Alimta), topoisomerase inhibitors and vinflunine act at different phases of the cell cycle and on folate metabolism. New agents that are combined with chemotherapy in urothelial cancer include the farnesyl transferase inhibitors and growth factors receptor inhibitors. Renal cell carcinoma (RCC) is particularly resistant to cytotoxic agents, although a gemcitabine/fluorinated pyrimidine combination may have modest but real clinical benefit. In metastatic RCC, new biologic and targeted therapies include anti-angiogenesis agents such as anti-vascular endothelial growth factor (VEGF) antibody and thalidomide, as well as toremifene, CCI-779 and allogeneic stem cell transplantation. Metastatic urothelial and renal cell cancers continue to be the clinical trial focus of many novel agents. The molecular biology of these diseases is being unravelled and as knowledge accumulates, our ability to target these cancers will continue to increase.