http://repub.eur.nl/res/aut/55221/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/35011/ 2012-01-10T00:00:00Z Purpose: This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy. Patients and Methods: The primary objective of the phase III part of this study was to compare the overall survival (OS) of chemotherapy-naive patients with measurable disease and an impaired renal function (glomerular filtration rate < 60 but > 30 mL/min) and/or performance score of 2 who were randomly assigned to receive either gemcitabine/carboplatin (GC) or methotrexate/carboplatin/ vinblastine (M-CAVI). To detect an increase of 50% in median survival with GC compared with M-CAVI (13.5 v 9 months) based on a two-sided log-rank test at error rates α .05 and β =.20, 225 patients were required. Secondary end points were overall response rate (ORR), progression-free survival (PFS), toxicity, and quality of life. Results: In all, 238 patients were randomly assigned by 29 institutions over a period of 7 years. The median follow-up was 4.5 years. Best ORRs were 41.2% (36.1% confirmed response) for patients receiving GC versus 30.3% (21.0% confirmed response) for patients receiving M-CAVI (P=.08). Median OS was 9.3 months in the GC arm and 8.1 months in the M-CAVI arm (P=.64). There was no difference in PFS (P=.78) between the two arms. Severe acute toxicity (death, grade 4 thrombocytopenia with bleeding, grade 3 or 4 renal toxicity, neutropenic fever, or mucositis) was observed in 9.3% of patients receiving GC and 21.2% of patients receiving M-CAVI. Conclusion There were no significant differences in efficacy between the two treatment groups. The incidence of severe acute toxicities was higher for those receiving M-CAVI.