Accelerated chemotherapy in the treatment of urothelial cancer

To evaluate an alternative treatment for advanced or metastatic urothelial cancers, a dose-intensive combination chemotherapy regimen using carboplati n, methotrexate, vincristine and cisplatin was given to 60 patients over a 3-year period (1990 to 1993). There were 26 patients with locally advanced disease and 34 with metastatic disease; 49 patients were evaluable for resp onse. A complete response was noted in four patients (8%) and a partial res ponse in 15 (31%), for an overall response rate of 39%. The median survival was 12 months. Two and 5-year survival rates were 25.5% (95% confidence in terval CI) 15.2-37.0) and 7.3% (95% CI 2.2-16.4) respectively. Failure-free survival was 15.3% (95% CI 7.5-25.6) at 2 years and 5.9% (95% CI 1.6-14.4) at 5 years, with a median of 8 months. For the responders, the median dura tion of response was 14 months, with a range of 2-59+ months. Toxicity incl uded myelosuppression (28% grade 4/5 neutropenia, 19% grade 4 thrombocytope nia), peripheral neuropathy (54% grade 1 and 23% grade 2/3) and ototoxicity (21% grade 1, 19% grade 2). This schedule of dose-intensified platinum-based chemotherapy for bladder c ancer resulted in significant neurotoxicity without evidence of enhanced re sponse rates or survival. Regimens such as methotrexate, vinblastine, doxor ubicin and cisplatin should remain standard. Accelerated regimens may be us eful in situations were it is necessary to administer chemotherapy over a s hort time (e.g. as part of combined modality treatment).