Vinflunine in Platinum-Pretreated Patients With Locally Advanced or Metastatic Urothelial Carcinoma: Results of a Large Phase 2 Study

• Published in: Cancer Vol. 115; no. 18; pp. 4110 - 4117
• Main Authors: VAUGHN, David J, SRINIVAS, Sandy, GEORGE, Claude, STADLER, Walter M, PILI, Roberto, PETRYLAK, Daniel, STERNBERG, Cora N, SMITH, David C, RINGUETTE, Sarah, DE WIT, Edwin, PAUTRET, Virginie
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 15-09-2009
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Carcinoma, Transitional Cell - drug therapy; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Male; Medical sciences; Middle Aged; Neoplasm Metastasis; Platinum Compounds - therapeutic use; Retreatment; Tumors; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Vinblastine - adverse effects; Vinblastine - analogs & derivatives; Vinblastine - therapeutic use; Antineoplastic agent; Human; Toxicity; Malignant tumor; Transitional cell carcinoma; Metastasis; Vinflunine; Chemotherapy; platinum-containing chemotherapy; Cancerology; Treatment; urothelial carcinoma; Platinum; Phase II trial; Advanced stage; Locally advanced stage; Cancer
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.24460

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.
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).
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.
Vinflunine demonstrates moderate activity in patients with platinum-pretreated UC. Toxicity is manageable and noncumulative.