To gather preliminary data on the tolerability of "stacking" sequentially applied regimens in patients recognized to have a poor prognosis from metastatic urothelial cancer. To assess toxicity, especially cumulative myelosuppression and peripheral neuropathy, and to characterize the median survival associated with this approach in a high-risk cohort. A total of ten patients were registered and treated. Eight of the 10 demonstrated a major response to treatment (3 patients with complete clinical response, 5 with partial response). The Kaplan-Meier estimate of median survival was 13.1 months, which is encouraging given the prognostic features of the group. Significantly, we did not appreciate excessive toxicity, and found no peripheral neuropathy of grade 3 or greater. We believe this experience supports the notion that combining individually optimized doublets or triplets will not necessarily be more toxic than multiple cycles of the same regimen. Furthermore, we are encouraged to pursue this line of research in light of promising levels of anti-cancer activity. It is clear however, that even complete responses are all too often short-lived, and that some qualitative change in the impact of cytotoxic therapy is required in order to substantially improve the survival of patients with metastatic urothelial cancer.