Actual experience and future development of gemcitabine in superficial bladder cancer

Gemcitabine has a molecular weight of 299 D, lower than that of commonly-used intravesical chemotherapeutic agents such as mitomycin C (389 D) and doxorubicin (589 D). This may enable gemcitabine to penetrate the bladder mucosa with beneficial effects in the treatment of early invasive bladder cancer (T1 disease). At the same time the molecular weight is high enough to prevent significant systemic absorption in an intact bladder. Based on the results of phase I studies, it appears that the 2000 mg dose of gemcitabine in 50/100 ml normal saline when administered intravesically for up to 2 h once a week for 6 weeks has unremarkable systemic and local side effects and therefore should be considered the most convenient schedule. The currently available phase II studies have assessed the activity of intravesical gemcitabine on a marker lesion in intermediate risk superficial bladder cancers (SBC), showing complete responses in up to 56% of cases. Few attempts have been made to test the activity of intravesical gemcitabine in high risk SBC achieving unexpected complete responses in BCG refractory CIS. Gemcitabine seems to have fulfilled the requirements to be a promising new candidate for standard intravesical therapy in SBC so far. Further phase II trials exploring the activity of gemcitabine on highly-recurrent intermediate risk or high risk SBC would provide additional information to foresee its efficacy in clinical practice and thus constitute the framework for large comparative phase III trials.