Advanced bladder/urothelial
cancer remains an incurable terminal disease, and accounts for 3% of the
cancer related mortality in the United States. Systemic
chemotherapy achieves palliation, survival benefit, and occasional long-term remissions. The two regimens that have been widely adopted consist of either
cisplatin and
gemcitabine, or the MVAC (
methotrexate,
vinblastine,
doxorubicin and
cisplatin) regimen. Novel
therapies are being evaluated in metastatic
bladder cancer to improve survival outcomes. A randomized trial of
larotaxel (a novel
taxane) and
cisplatin vs
cisplatin and
gemcitabine in frontline
therapy of metastatic urothelial
cancer is ongoing. The studies evaluating
therapies targeted frontline involve
cisplatin and
gemcitabine with or without
cetuximab (ongoing), and with or without
bevacizumab (CALGB proposed trial). With the advent of adjuvant/neoadjuvant
cisplatin-based
therapy, and improvement in supportive care, more patients are being considered for second-line
therapies in urothelial
cancer thus making this a field of emerging importance. The only phase III trial in pretreated urothelial
cancer compared
vinflunine with best supportive care, and revealed no significant survival improvement. Clinical trials are ongoing with
pazopanib, a
VEGF inhibitor, and
Zactima, a
VEGF and EGFR inhibitor. The biggest hurdle to progress in advanced
bladder cancer has been the slow accrual to studies in the United States. Making clinical trial participation a priority in
bladder cancer is the dire need of the moment. At the same time, it is essential to take into account the changing needs of the population afflicted with
bladder cancer, and tailor the therapeutic trials to fit a contemporary patient.