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Objective: To estimate the response rate of gemcitabine, paclitaxel, and doxorubicin in patients with advanced urothelial carcinoma, we conducted a phase II clinical trial. Patients with renal insufficiency cannot receive standard cisplatin-based chemotherapy for urothelial carcinoma, and carboplatin-based regimens have proved unsatisfactory. Secondary end points for this study included overall survival, safety of the regimen, and safety of same-day pegfilgrastim dosing.Methods: A two-stage design was chosen with target response rate of 40%. Key inclusion criteria were metastatic or unresectable urothelial carcinoma, no prior chemotherapy, glomerular filtration rate <60 mL/min, and no dialysis. Gemcitabine (900 mg/m(2)), paclitaxel (135 mg/m(2)), and doxorubicin (40 mg/m(2)) were administered on day 1 of each 14-day cycle. Pegfilgrastim was given with every cycle on either day 1 or optionally day 2.Results: Forty patients were enrolled and 39 were treated. Median age was 72 years (range 51-89). There were 7 complete and 15 partial responses, for a response rate of 56.4% (95% confidence interval, 39.6-72.2). Most cycles (82.8%) were given with same-day pegfilgrastim. Notable grade 3 and 4 nonhematologic toxicities were fatigue and mucositis (10.3% each). There were 4 episodes of neutropenic fever (4 of 198 cycles [2%]; 4 of 39 patients [10.3%]) and no treatment-related deaths. Median overall survival was 14.4 months.Conclusion: The combination of gemcitabine, paclitaxel, and doxorubicin is effective first-line chemotherapy for patients with advanced urothelial carcinoma and renal insufficiency. Neutropenic prophylaxis was acceptable whether pegfilgrastim was given immediately or 24 hours after chemotherapy. [ABSTRACT FROM AUTHOR]