Intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer-mediated malignant pleural effusion

Abstract

Malignant pleural effusion (MPE) is a common complication of advanced non-small cell lung cancer (NSCLC). Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been shown to be efficient in suppressing the accumulation of pleural fluid. However, whether intrapleural delivery of bevacizumab can be used to treat MPE remains unknown. The aim of the present study was to evaluate the efficacy and safety of combined intrapleural therapy with bevacizumab and cisplatin, an antineoplastic agent, in controlling MPE. A total of 72 NSCLC study subjects with MPE were randomly assigned to one of two groups. The first group received intrapleural bevacizumab (300 mg) with cisplatin (30 mg) therapy and the second group received intrapleural cisplatin (30 mg) therapy alone. Pleural fluid was collected from both groups prior to and following treatment. The levels of VEGF and carcinoembryonic antigen (CEA) in the pleural fluid were determined by ELISA. In 70 evaluable study subjects, the curative efficacy in the bevacizumab group was significantly higher than that found in the cisplatin group (83.33 vs. 50.00%, respectively; p<0.05). Therapy with combined bevacizumab plus cisplatin significantly reduced VEGF levels in the pleural fluid (p<0.01). In the bevacizumab group, the levels of VEGF in the pleural fluid were significantly lower compared to those of the cisplatin group after treatment, which showed greater efficacy (p<0.01). In addition, combination therapy showed greater efficacy in the patients with high levels of VEGF expression (p<0.01). There was no significant difference in grade III/IV adverse events between the two groups. All procedures were well tolerated by the patients. Combined intrapleural therapy with bevacizumab and cisplatin was effective and safe in managing NSCLC-mediated MPE. We propose that VEGF expression levels in MPE could serve as a prognostic marker for bevacizumab therapy.

Malignant Pleural Effusion and ascites Induce Epithelial-Mesenchymal Transition and Cancer Stem-like Cell Properties via the Vascular Endothelial Growth Factor (VEGF)/Phosphatidylinositol 3-Kinase (PI3K)/Akt/Mechanistic Target of Rapamycin (mTOR) Pathway

“…So far, there are no reports that mTOR inhibitors were used for malignant PE/ascites management even though some of them are available clinically, whereas the efficacy of anti-VEGF therapy with bevacizumab, a VEGF antibody, by intrapleural or intraperitoneal administration for malignant PE/ascites has been frequently reported (47)(48)(49). One mechanism of bevacizumab is that it reduces vascular permeability induced by VEGF (50).…”

Differential expression of vascular endothelial growth factor-A, -C and -D for the diagnosis and prognosis of cancer patients with malignant effusions

“…Previous studies have demonstrated that elevated levels of vascular endothelial growth factor (VEGF), tumor angiogenesis and increased vascular permeability following tumor invasion or metastasis to the pleuroperitoneum are important mechanisms of serous cavity effusions. VEGF requires further study due to its presence in the pleural fluid and its potential use as a therapeutic target (3)(4)(5).…”

“…Multiple clinical studies have also demonstrated the potential benefit of VEGF-A inhibition in patients with malignant effusions (15). Anti-angiogenic therapy (such as bevacizumab, a monoclonal antibody targeting VEGF-A) adjuvant to chemotherapy serves a potential function in the management of pleural effusions in advanced non-squamous non-small cell lung cancer (5,16).…”

Prognostic Values of VEGF and Endostatin with Malignant Pleural Effusions in Patients with Lung Cancer

“…Some angiogenesis inhibitors such as Bevacizumab, a recombinant humanized monoclonal antibody to VEGF, and Endostar, a modified and recombinant human endostatin, either intravenously or intrapleurally, when combined with chemotherapy, have been shown to be efficient in suppressing the accumulation of pleural fluid (Hama et al, 2011;Kitamura et al, 2013;Du et al, 2013). reported that VEGF levels in MPE could serve as a prognostic marker for bevacizumab therapy.…”