A randomized clinical study to compare intrapleural infusion with intravenous infusion of bevacizumab in the management of malignant pleural effusion in patients with non‐small‐cell lung cancer

Abstract

BackgroundTo compare the efficiency and toxicity of bevacizumab by intrapleural or intravenous infusion in the management of malignant pleural effusion in patients with non‐small‐cell lung cancer (NSCLC).MethodsSensitizing mutation negative NSCLC patients with malignant pleural effusion were randomized into two groups in 1:1 ratio. The pleural effusion was completely drained in 24 hours; one group received intrapleural infusion and the second group received intravenous infusion of bevacizumab at a dose of 7.5 mg per kg bodyweight. The serum vascular endothelial growth factor (VEGF) was tested before and 72 hours after injection of bevacizumab. Computerized tomography (CT) scan to evaluate pleural effusions was carried out at four weeks for each patient and their survival followed‐up.ResultsA total of 67 patients were screened and 43 enrolled into the study. The response rate was 80% (16 of 20) in the intrapleural group and 66.7% (14 of 21) in the intravenous group. The median duration of response (DoR) of pleural effusion was 4.50 months and 3.70 months, respectively. The median serum VEGF level at 72 hours decreased 67.25% in the intrapleural group and 57.19% in the intravenous group compared to baseline level (P = 0.276). The median serum VEGF level at 72 hours decreased 52.02% compared to baseline level in patients’ DoR less than three months and 68.33% in patients' DoR longer than three months, respectively (P = 0.014). The main side effects noted were mild to moderate hypertension, proteinuria and epistaxis.ConclusionsBevacizumab intrapleural infusion had higher efficiency and higher safety than intravenous infusion in the management of malignant pleural effusion caused by NSCLC. The decreased level of serum VEGF at 72 hours after bevacizumab treatment was closely related to the response rate and duration of the response of pleural effusion.

Novel therapies for malignant pleural effusion: Anti‑angiogenic therapy and immunotherapy (Review)

“…Hypertension, epistaxis and proteinuria are common AEs associated with bevacizumab, which occurred more often in the intravenous group compared with in the intrapleural one (13). A higher ORR and a longer median duration of response were also observed in the intrapleural group, but the difference between the two groups was not statistically significant (13). The reason for this may be that the sample size of the study was too small (n=43).…”

“…Role of VEGF in MPE. Large amounts of VEGF can be produced as tumor cells invade into the pleura, resulting in the acceleration of vascular permeability (13). The pleural fluid VEGF levels in MPE are significantly higher than those in effusions of benign disease, such as congestive heart failure and tuberculosis (2,8,14).…”

“…Several studies have specifically researched the efficacy and safety of bevacizumab for the management of MPE (Table I). Among them, 6 are prospective studies (13,(24)(25)(26)(27)(28), including two phase II trials conducted by Japanese groups (24,25). Unfortunately, there is still a lack of evidence from large phase III trials to confirm the effect of bevacizumab in the management of MPE.…”

“…Furthermore, the closed nature of the pleural space makes it an ideal site for intrapleural infusion (10). A recent randomized clinical study compared the efficiency and safety of intrapleural (7.5 mg/kg) and intravenous (7.5 mg/kg) infusion of bevacizumab in the management of MPE (13). Hypertension, epistaxis and proteinuria are common AEs associated with bevacizumab, which occurred more often in the intravenous group compared with in the intrapleural one (13).…”

“…A recent randomized clinical study compared the efficiency and safety of intrapleural (7.5 mg/kg) and intravenous (7.5 mg/kg) infusion of bevacizumab in the management of MPE (13). Hypertension, epistaxis and proteinuria are common AEs associated with bevacizumab, which occurred more often in the intravenous group compared with in the intrapleural one (13). A higher ORR and a longer median duration of response were also observed in the intrapleural group, but the difference between the two groups was not statistically significant (13).…”