title: Eastern Cooperative Oncology Group phase II trial of ifosfamide in the treatment of previously treated advanced urothelial carcinoma.
abstract: OBJECTIVE
  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 and their toxicity spectra. Here we report results from the use of IFX in this population.
  
  
  METHODS
  Ambulatory patients with advanced urothelial carcinoma were treated with IFX 3,750 mg/m2 and mesna 2250 mg/m2 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/m2 IV with mesna 750 mg/m2 IV for 5 days every 3 weeks. Doses were modified for hematologic, renal, and CNS toxicity.
  
  
  RESULTS
  Of 56 eligible patients entered onto the study, 26 received the 2-day schedule and 30 were treated on the 5-day regimen. All patients had progressive disease following prior systemic chemotherapy. There were five complete responses (CRs) and six partial responses (PRs) for an overall response rate of 20% (exact 95% confidence interval [CI], 10% to 32%). Renal and CNS toxicity was severe before the change in schedule, but manageable after the change. Major identified toxicities were gastrointestinal, myelosuppressive, renal, and CNS. There were four early deaths to which treatment probably contributed, but were multifactorial in etiology.
  
  
  CONCLUSIONS
  IFX has significant activity, but also major toxicity in a heavily cisplatin-pretreated cohort with advanced urothelial carcinoma. A modification of dose and/or schedule from that described should be considered in future trials. Combination regimens using this agent should be explored.
authors.affiliation: Gundersen Clinic, Ltd, La Crosse, WI 54601, USA. RWITTE@GC.GUNDLUTH.ORG
authors.forename: R S
authors.initials: RS
authors.lastname: Witte
authors.forename: P
authors.initials: P
authors.lastname: Elson
authors.forename: B
authors.initials: B
authors.lastname: Bono
authors.forename: R
authors.initials: R
authors.lastname: Knop
authors.forename: R R
authors.initials: RR
authors.lastname: Richardson
authors.forename: R
authors.initials: R
authors.lastname: Dreicer
authors.forename: P J
authors.initials: PJ
authors.lastname: Loehrer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide