Intrapleural Administration With Rh-Endostatin and Chemical Irritants in the Control of Malignant Pleural Effusion: A Systematic Review and Meta-Analysis

Abstract

IntroductionA modified and recombinant human endostatin (Rh-endostatin) is often used in the control of malignant pleural effusion (MPE) through intrapleural infusion.ObjectivesTo demonstrate the clinical response, survival, and safety of Rh-endostatin plus chemical irritants, their optimal combinations, treatment threshold, and optimal usage, we performed a new systematic review and meta-analysis.MethodologyAll randomized controlled trials (RCTs) were collected from Chinese and English electronic databases (from inception until August 2020). We pooled the data using a series of meta-analyses and summarized the evidence quality following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsWe included 75 RCTs recruiting 4,678 patients, which reported six combinations for Rh-endostatin plus chemical irritants. Among the six combinations, only Rh-endostatin plus cisplatin (DDP) with enough trials might improve the complete response [2.29 (1.93, 2.71)] and quality of life [3.01 (2.49, 3.63)] and reduce treatment failure [0.29 (0.25, 0.33)] and progressive disease [0.27 (0.22, 0.34)]. It might not increase the risk of adverse drug reactions. For patients with lung cancer, moderate to massive effusion, initial treatment, Karnofsky Performance Status (KPS) score ≥60, or anticipated survival time ≥3 months, Rh-endostatin (30–45 mg each time, once or twice a week 3–4 times) plus DDP (30–60 mg/m2) obtained a significant improvement in clinical response and a reduction of failure and progressive disease. Most results had good robustness and moderate quality.ConclusionsCurrent evidence suggests that Rh-endostatin with DDP may be an optimal combination, which may improve clinical response and reduce failure and progressive disease with good safety. Rh-endostatin (30–40 mg each time, once or twice a week 3–4 times) with DDP (30–40 mg/m2) may be an optimal usage for achieving an ideal response.

Intrapleural Perfusion With Staphylococcal Enterotoxin C for Malignant Pleural Effusion: A Clustered Systematic Review and Meta-Analysis

“…The clinical responses were measured by using a complete response (CR), pleurodesis failure, and disease progression (DP). Integrating previous criteria ( 6 , 9 , 25 – 27 ), the CR is defined as a pleural fluid disappeared for more than 1 month, or the lack of accumulation of fluid; the partial response (PR) is a pleural fluid reduced more than 50% for more than 1 month; the no response (NR)/stable disease (SD) is pleural fluid reduced <50% or increased <25% or the pleural fluid recurred but required no further therapy; and the DP is pleural fluid increased more than 25% along with other signs of progression or symptomatic re-accumulation of the effusion, requiring repeat thoracentesis or chest tube. Accordingly, the pleurodesis failure was defined as NR or SD plus DP.…”

“…So, we classified the heterogeneity as significant and potential clinical heterogeneity. On the basis of the principle of evidence classification ( 23 ) and our previous experiences ( 6 , 9 ), we systematically collected and evaluated all available randomized controlled trials (RCTs), implemented topic clustering to obtain serial homogeneous perfusion protocols, and analyzed the data from each protocol using the meta-analysis or descriptive analysis. Then, we implemented a subgroup analysis to deal with the potential heterogeneity for main protocol.…”

“…Otherwise, the pool was abandoned, and a forest graph was adopted to describe the results. Following previous guidance ( 35 ) and our experiences ( 6 , 9 ), a subgroup analysis model was developed to reveal the potential heterogeneity between different trials and determine the effects of variables on clinical responses. The variables were patient baselines, usages of SEC or chemical agents, an evaluation criterion, and published time.…”

“…The trial was defined as an over or underestimation when the result was significant difference, and beneficial to SEC perfusion. A sensitivity analysis model was developed to evaluate the robustness ( 6 ). Before and after rejecting all the trials with poor quality and over-estimation, if the result had good uniformity , the outcome was good robustness.…”

“…Malignant pleural effusion (MPE) is a common manifestation of malignant tumors and a significant source of cancer morbidity and mortality, which often causes progressive breathlessness, short survival, and poor quality, and requires palliation ( 1 , 2 ). So far, the pleurodesis has remained the cornerstone of treatment, and the pleurodesis agents include chemical agents ( 3 – 5 ), biologic response modifiers ( 6 , 7 ), and traditional Chinese medicine injections (TCMIs) ( 8 , 9 ), etc. As important biologic response modifiers , serial bio-products from Staphylococcus aureus ( S. aureus ) ( 10 ), hemolytic streptococcialpha ( 11 , 12 ), corynobactum parvum ( C. parvum ) ( 13 ), and streptococcus pyogenes ( S. pyogenes ) ( 14 ) have been used in clinical studies to achieve pleurodesis and control fluid recurrence.…”