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Abstract:
Recent data from Phase II trials in patients with advanced transitional cell carcinoma of the urothelial tract suggest combination chemotherapy regimens are inducing a higher number of complete remissions (CR), and an overall response rate between 50% and 70%. Most active combination regimens are cisplatin + methotrexate based or cisplatin + Adriamycin (doxorubicin) based. As single agents, cisplatin has a response rate of 30% in 320 patients, methotrexate, 29% in 236 cases, and Adriamycin, 17% in 248 cases. With each drug used singly, however, complete response is uncommon. Other active single agents include vinblastine (16% in 38 cases) and mitomycin C (13% in 42 cases). New agents being evaluated which show some promise include gallium nitrate, carboplatinum, and other antifols. In a trial by the Northern California Oncology Group which evaluated a combination of cisplatin, methotrexate, and vinblastine (CMV), 28% of 50 cases achieved a CR lasting 44 weeks, and 28% a partial remission (PR) sustained for 29 weeks. A limited number of cases required surgical debulking for obtainment of CR status. At the University of Michigan, a trial of cisplatin and dichloromethotrexate induced responses in over 60% of cases. The regimen of methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC) has been reported to induce CR in 37% of cases, and PR in an additional 31%. In the latter trial at Memorial Hospital in over 100 cases with bidimensionally measurable advanced disease, the median survival of CR has not yet been reached at 28 months, whereas those who achieve PR survive 12 months versus 6 months for nonresponders. Indirectly, the success of such combination regimens is apparent from the increasing number of central nervous system relapses, without systemic recurrence, in complete responders. Additional data indicate that cisplatin + methotrexate, without the addition of other drugs, is also an active regimen. The attainment of CR in 20% to 40% of cases given these multidrug regimens has led to adjuvant and neoadjuvant protocols. Although results of randomized prospective trials have not yet been reported, preliminary Phase II data are promising.