Progress in the chemotherapy of metastatic cancer of the urinary tract

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Abstract
Cytotoxic chemotherapy has an evolving role in the management of metastatic cancer of the bladder and urinary tract. The most responsive of these tumors are transitional cell carcinomas. Standard single agents (e.g., methotrexate, doxorubicin, mitomycin, ifosfamide, vinblastine, and cisplatin) have produced objective response rates of 15-25% and combination chemotherapy has resulted in objective regression in 40-75% of cases. The taxanes and gemcitabine are now being incorporated into combination regimens because they have activity against this disease, both in previously treated and untreated patients. In previously untreated patients, regimens incorporating gemcitabine and paclitaxel and a platinum complex, with or without ifosfamide or doxorubicin, produce median survival periods of 15-20 months. Contemporary experience with the methotrexate/vinblastine/doxorubicin/cisplatin regimen yields a median survival period of 18 months. Traditional cytotoxic regimens have been ineffective in the management of adenocarcinoma and squamous cell carcinoma of the bladder. However, regimens predicated on the taxanes and gemcitabine yield response rates of 30-40%, which may translate into improved survival. Nevertheless, stage migration may produce the semblance of improved survival, which may reflect reduced tumor burden (via reclassification) and case selection. Because historically controlled comparisons may introduce errors from case selection bias, stage migration, differences in duration of follow-up, and the evolution of supportive care, it is essential to validate the role of new agents in well structured, randomized clinical trials.