title: Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: results of a large phase 2 study.
abstract: BACKGROUND
  The activity and safety of vinflunine was evaluated in patients with locally advanced or metastatic urothelial carcinoma (UC) who developed disease progression within 12 months of platinum-containing chemotherapy.
  
  
  METHODS
  Patients with UC were eligible if they received a prior platinum-based regimen in the neoadjuvant/adjuvant setting or as first-line treatment for advanced/metastatic disease and had developed disease progression within 12 months. Vinflunine was administered intravenously every 3 weeks. Patients with Karnofsky performance status of 80 or 90, impaired renal function, prior pelvic irradiation, or age>or=75 years received an initial dose of 280 mg/m2, which was escalated to 320 mg/m2 in Cycle 2 if well tolerated. All other patients received an initial dose of 320 mg/m2. The primary endpoint was response rate defined by an independent response review committee (IRRC).
  
  
  RESULTS
  Per the IRRC, 22 patients achieved a partial response, with a response rate of 15% (95% confidence interval, 9%-21%) with a median duration of response of 6.0 months. Sixty-four (42%) patients had stable disease. The median progression-free survival was 2.8 months, and the median overall survival was 8.2 months. Myelosuppression was the most frequent adverse event, with grade 3 of 4 (adverse events were evaluated according to the National Cancer Institute Common Toxicity Criteria [version 2.0] guidelines) neutropenia reported in 58% of the patients. Grade 3 of 4 febrile neutropenia occurred in 10 (7%) patients. Nonhematologic treatment-related events (grade 3 of 4) were generally manageable and included constipation (17%), asthenia/fatigue (13%), ileus (5%), and abdominal pain (5%). No cumulative toxicity was observed.
  
  
  CONCLUSIONS
  Vinflunine demonstrates moderate activity in patients with platinum-pretreated UC. Toxicity is manageable and noncumulative.
authors.affiliation: Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. david.vaughn@uphs.upenn.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Vaughn
authors.forename: Sandy
authors.initials: S
authors.lastname: Srinivas
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.forename: Daniel
authors.initials: D
authors.lastname: Petrylak
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: David C
authors.initials: DC
authors.lastname: Smith
authors.forename: Sarah
authors.initials: S
authors.lastname: Ringuette
authors.forename: Edwin
authors.initials: E
authors.lastname: de Wit
authors.forename: Virginie
authors.initials: V
authors.lastname: Pautret
authors.forename: Claude
authors.initials: C
authors.lastname: George
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017671:Platinum Compounds / Q000627:therapeutic use; D019233:Retreatment; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D017671:Platinum Compounds; C111217:vinflunine; D014747:Vinblastine