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

Invest New Drugs. 2007 Apr;25(2):181-5. doi: 10.1007/s10637-006-9009-4. Epub 2006 Sep 16.


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.

Patients and 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).

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Boronic Acids / adverse effects
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Survival Analysis
  • Urologic Neoplasms / drug therapy*
  • Urologic Neoplasms / pathology
  • Urothelium / pathology


  • Antineoplastic Agents
  • Boronic Acids
  • Pyrazines
  • Bortezomib