Cisplatin and methotrexate used singly are the most active agents against transitional cell carcinoma of the urothelium, inducing remission in approximately 30% of cases. Other agents demonstrating some activity include vinblastine, vincristine, and, to a lesser extent, fluorouracil, mitomycin C, and amsacrine. Most multidrug combinations have not proven to be more effective than single-drug therapy; however, there is some indication that response and percent of complete remission (CR) is increased with cisplatin plus doxorubicin, and with CMV (cisplatin, methotrexate, vinblastine) and M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) regimens. With the latter two regimens, approximately 20% to 35% of cases achieve CR that persists in selected cases for 2 to 4 years. Such results against advanced transitional cell carcinoma with CMV and M-VAC have led to their use in neoadjuvant trials for this chemotherapeutically responsive tumor.