Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: results of a large phase 2 study.

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.

Clinical activity of vinflunine in transitional cell carcinoma of the urothelium and other solid tumors.

Vinflunine is a novel microtubule inhibitor of the vinca alkaloid class currently in development for the treatment of advanced transitional cell carcinoma of the urothelium (TCCU) and other solid tumors. This review summarizes the clinical activity of vinflunine as a single agent or in combination with other antineoplastic drugs. Vinflunine is active against a variety of tumor types, including advanced TCCU, metastatic breast cancer, advanced non-small cell lung cancer, and malignant pleural mesothelioma. It has a manageable and noncumulative toxicity profile, and its specific mechanism of action has been linked to a reduced potential for peripheral sensory neuropathy. The activity and tolerability of this agent warrant further investigation. Phase 3 trials are underway to further define the extent of clinical benefit provided by vinflunine in patients with advanced solid malignancies.