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: David J Vaughn, Sandy Srinivas, Walter M Stadler, Roberto Pili, Daniel Petrylak, Cora N Sternberg, David C Smith, Sarah Ringuette, Edwin de Wit, Virginie Pautret, Claude George
• Journal: Cancer (Cancer) Vol. 115 Issue 18 Pg. 4110-7 (Sep 15 2009) ISSN: 0008-543X [Print] United States
• PMID: 19536904 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: Copyright (c) 2009 American Cancer Society.

Chemical References

• Antineoplastic Agents
• Platinum Compounds
• vinflunine
• Vinblastine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Transitional Cell (drug therapy)
• Disease Progression
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Platinum Compounds (therapeutic use)
• Retreatment
• Urinary Bladder Neoplasms (drug therapy, pathology)
• Vinblastine (adverse effects, analogs & derivatives, therapeutic use)