Phase II study of vinflunine in malignant pleural mesothelioma.
Talbot DC., Margery J., Dabouis G., Dark G., Taylor H., Boussemart H., Cadic V., Pinel M-C., Rivière A., Ollivier L., Ruffié P.
PURPOSE: Malignant pleural mesothelioma (MPM) is a disease of increasing incidence for which treatment options are limited. This study reports the clinical efficacy data for vinflunine, a novel microtubule inhibitor, in MPM. PATIENTS AND METHODS: Patients with a histologically confirmed diagnosis of MPM were eligible for enrollment onto this multicenter phase II trial if they had not received prior chemotherapy or radiotherapy and had measurable lesions by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Vinflunine 320 mg/m2 by 10-minute intravenous infusion was administered on day 1 of 21-day cycles. Modifications of dose and schedule were made according to National Cancer Institute Common Toxicity Criteria version 2.0. Efficacy was assessed by an external, independent radiologist. The one-sample multiple testing procedure of Fleming was applied at the predetermined recruitment stages of 20 and 40 assessable patients. RESULTS: Sixty-seven patients were enrolled. Five patients were not assessable for tumor response. The response rate was 13.8% (95% CI, 6.5% to 24.7%). The median survival was 10.8 months (95% CI, 7.8 to 12.0 months). The most common adverse events were anemia, neutropenia, fatigue, constipation, and nausea. Of grade 3 and 4 toxicities, neutropenia and constipation were the most common (45% and 9% of patients, respectively). CONCLUSION: Vinflunine can be delivered with high-dose intensity in patients with MPM. The response rate and median survival are encouraging for a single agent. These data suggest that vinflunine should be further evaluated in the management of MPM.