title: A phase II study of PS-341 (Bortezomib) in advanced or metastatic urothelial cancer. A trial of the Princess Margaret Hospital and University of Chicago phase II consortia.
abstract: BACKGROUND
  Based on evidence of activity in epithelial tumors in preclinical and Phase I studies, its novel mechanism of action, and its tolerability we undertook a study of bortezomib [PS-341], a reversible proteasome inhibitor, for patients with advanced or metastatic urothelial cancer.
  
  
  METHODS
  Patients with advanced or metastatic unresectable urothelial carcinoma were enrolled onto this multicenter, phase II trial. Patients with measurable disease were treated with bortezomib 1.3 mg/m2/day (twice weekly for 2 weeks out of 3) by intravenous infusion on days 1, 4, 8, and 11 every 21 days. A two stage phase II design was used.
  
  
  RESULTS
  Twenty-one patients were enrolled and twenty were eligible and received treatment. Eighty-five percent of patients had previous chemotherapy regimens. No objective responses were observed, median time-to-progression was 8.1 weeks (95% confidence interval [CI] 6.4 to 9), and median overall survival is estimated to be 15 weeks (95% CI 3.6 - NA). A total of 15 patients experienced a grade 3-4 adverse event. The most common were alkaline phosphatase (20% patients), lymphopenia (20% patients), myalgia (15% patients), dyspnea (15% patients) and thrombosis/embolism (15% patients).
  
  
  CONCLUSIONS
  Single-agent bortezomib is an ineffective treatment for progressive-cisplatin-refractory urothelial carcinoma and should not be considered for future clinical trials in this population of patients.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gomez-Abuin
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Greg
authors.initials: G
authors.lastname: Pond
authors.forename: Pamela
authors.initials: P
authors.lastname: Degendorfer
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib