Vandetanib and Indwelling Pleural Catheter for Non-Small-Cell Lung Cancer With Recurrent Malignant Pleural Effusion

We report the final results of a single-arm phase II clinical trial of the vascular endothelial growth factor (VEGF) receptor inhibitor, vandetanib, combined with intrapleural catheter placement in 20 patients with non-small-cell lung cancer and recurrent malignant pleural effusion, to determine whether vandetanib reduces time to pleurodesis. Vandetanib therapy was well tolerated; however it did not significantly reduce time to pleurodesis. Introduction/Background: Non-small-cell lung cancer patients with malignant pleural effusion have a poor overall median survival (4.3 months). VEGF is a key regulator of pleural effusion production. It is unknown if pharmacological inhibition of VEGF signaling modifies the disease course of non-small-cell lung cancer patients with recurrent malignant pleural effusion. We report the final results of a single-arm phase II clinical trial of the VEGF receptor inhibitor, vandetanib, combined with intrapleural catheter placement in patients with non-small-cell lung cancer and recurrent malignant pleural effusion, to determine whether vandetanib reduces time to pleurodesis. Patients and Methods: Non-small-cell lung cancer patients with proven metastatic disease to the pleural space using pleural fluid cytology or pleural biopsy who required intrapleural catheter placement were eligible for enrollment. On the same day of the intrapleural catheter insertion, the patients were started on a daily oral dose of 300 mg vandetanib, for a maximum of 10 weeks. The primary end point was time to pleurodesis, with response rate as the secondary end point. Exploratory analyses included measurement of pleural fluid cytokines and angiogenic factors before and during therapy. Results: Twenty eligible patients were included in the trial. Eleven patients completed 10 weeks of treatment. Median time to pleurodesis was 35 days (95% confidence interval, 15-not applicable). Median time to pleurodesis in the historical cohort was 63 days (95% confidence interval, 45-86) when adjusted for Eastern Cooperative Oncology Group performance status <= 2. Conclusion: Vandetanib therapy was well tolerated; however, it did not significantly reduce time to pleurodesis.