Gemcitabine doublets in advanced urothelial cancer

Gemcitabine was identified as an active agent in the treatment of urothelial cancer early in its clinical development. A gemcitabine/cisplatin regimen has been shown to lead to comparable survival in a phase III comparison to methotrexate/vinblastine/doxorubicin/cisplatin in the metastatic setting with less toxicity. Nonetheless, cisplatin-related toxicity is not inconsequential. Renal insufficiency limits wide applicability and long-term survival remains poor. A number of additional doublet combinations have thus been investigated. Substitution of carboplatin for cisplatin is feasible but leads to an apparent lower complete response rate. Likewise, combinations of gemcitabine and a taxane are feasible, but with somewhat discouraging response rates. A combination of doxorubicin and gemcitabine has been reported to lead to a 36% complete response rate, but this has not been confirmed. Combinations with targeted therapeutic agents such as the epidermal growth factor receptor inhibitors and trastuzumab have great potential, but the clinical studies have not yet been completed.