EASTERN-COOPERATIVE-ONCOLOGY-GROUP PHASE-II TRIAL OF IFOSFAMIDE IN THE TREATMENT OF PREVIOUSLY TREATED ADVANCED UROTHELIAL CARCINOMA

Purpose: Alkylating agents have modest activity in advanced urothelial carcinoma, Ifosfamide (IFX) is an agent as yet unstudied in advanced urothelial carcinoma, Despite recent advances in the treatment of this disease, there continues to be a need to identify new active agents a nd their toxicity spectra, Here we report results from the use of IFX in this population, Patients and Methods: Ambulatory patients with adv anced urothelial carcinoma were treated with IFX 3,750 mg/m(2) and mes na 2250 mg/m(2) both intravenously (IV) daily for 2 days every 3 weeks , Significant renal and CNS toxicity required a dose change of IFX to 1,500 mg/m(2) IV with mesna 750 mg/m(2) IV for 5 days every 3 weeks. D oses were modified for hematologic, renal, and CNS toxicity.Results: O f 56 eligible patients entered onto the study, 26 received the 5-day s chedule and 30 were treated on the 5-day regimen, All patients had pro gressive disease following prior systemic chemotherapy. There were fiv e complete responses (CRs) and six partial responses (PRs) for an over all response rate of 20% (exact 95% confidence interval [CI], 10% to 3 2%). Renal and CNS toxicity was severe before the change in schedule, but manageable after the change, Major identified toxicities were gast rointestinal, myelosuppressive, renal, and CNS. There were four early deaths to which treatment probably contributed, but were multifactoria l in etiology. Conclusion: IFX has significant activity, but also majo r toxicity in a heavily cisplatin-pretreated cohort with advanced urot helial carcinoma. A modification of dose and/or schedule from that des cribed should be considered in future trials, Combination regimens usi ng this agent should be explored. (C) 1997 by American Society of Clin ical Oncology.