The intrapleural administration with thymic peptides in malignant pleural effusion: A clustered systematic review and meta-analysis

Background: Thymic peptides (TPs) are often used to control malignant pleural effusion (MPE). So, we performed a clustered systematic review and meta-analysis to clarify the treatment regimens of TPs for MPE, demonstrate their clinical effectiveness and safety, and reveal the indications and optimal usage for a desired effectiveness. Materials and methods: We collected all trials of TPs for MPE from Chinese and English databases (from inception until May 2021). After evaluating their bias risk, we pooled the data from each regimen using the meta-analysis or descriptive analysis, and summarized the evidence quality using the Grading of Recommendation Assessment, Development and Evaluation approach (GRADE). Results: Thirty-four trials were clustered into TPs for MPE from lung cancer or miscellaneous tumors. The TPs combined with chemical agents were mainly used in MPE from lung cancer. All five regimens, only thymosin with oxaliplatin (L-OHP) significantly improved the complete response (CR) [2.40 (1.84 to 3.13)], quality of life [2.04 (1.20 to 3.48)], 0.5- and 1-year overall survival (OS) rate [5.75 (3.02 to 10.92) and 5.29, (1.71 to 16.36)]. It also up-regulated the T lymphocyte levels, and reduced the pleurodesis failure, disease progression and adverse events. In patients with moderate to large volume, Karnofsky Performance Status score >= 50 or anticipated survival time >= 3 months, the thymosin (300 mg/time, one time/week and lasting two to eight times) with oxaliplatin (100 mg/m(2)) achieved a desired response. Most results were moderate quality. Conclusions: The current evidences indicate that the TPs are important pleurodesis agents, which combination with chemical agents are mainly used in MPE from lung cancer. The thymosin with L-OHP is a main regimen, which shows a significant improvement in clinical responses, antitumor immunity, and with a reasonable security. The evidence also provides indications and optimal usage for achieving a desired effectiveness.