A novel agent, p-toluenesulfonamide, in the management of malignant pleural effusions

Abstract

Background: Malignant pleural effusion (MPE) is the lethal consequence of various human cancers metastatic to the pleural cavity, with unclear underlying mechanisms and limited effective treatments. Current therapies, such as talc insufflation, effectively achieve pleurodesis but result in irreversible pleural adhesion, significantly impacting patient quality of life. Para-toluenesulfonamide (PTS), a small molecule, has demonstrated anticancer activity in preclinical and clinical studies.

Methods: To evaluate the safety and efficacy of PTS for MPE treatment, we conducted preclinical and clinical exploratory studies.

Results: In a mouse MPE model, intrapleural injection of PTS significantly reduced effusion volume and pleural tumor weight without causing pleural adhesions or loculation. Clinical studies in China and Taiwan further supported these findings. In China, 17 patients treated with intrapleural PTS achieved an MPE response rate of 76.5 % at treatment completion and 41.2 % maintained control at four weeks post-treatment. Quality of life, assessed by FACT-L scores, improved significantly without serious adverse events. In Taiwan, seven lung cancer patients treated with intrapleural PTS showed significant reduction in drained effusion volume from baseline to 30 days post-treatment. The MPE response rate was 85.7 %, with a disease control rate of 100 %. The median time to reintervention was 84 days, with no observed pleural adhesions or serious adverse effects.

Conclusion: Collectively, these results indicate that PTS effectively inhibits tumor growth, reduces MPE accumulation, and avoids pleural adhesion, highlighting its potential as a promising therapeutic option for managing MPE. Further comprehensive studies are warranted to establish its clinical role.

Keywords: Intrapleural; Local administration; Malignant pleural effusion; Para-toluenesulfonamide; Pleural adhesions.