A novel agent, para-toluenesulfonamide, for the management of malignant pleural effusions.

Abstract

e15139 Background: Malignant pleural effusion (MPE) is the lethal consequence of various human cancers. No effective agents are currently available to cure MPE. Para-toluenesulfonamide (PTS) is a small molecule and was reported to demonstrate potential activity in treating lung cancer. To assess the safety and efficacy of PTS for treating MPE, we conducted a study using intrapleural PTS injections in mice. To validate the findings, we further conducted a single-arm exploratory study, using PTS to treat MPE in lung cancer patients. Methods: To verify PTS's MPE-reducing activity, its efficacy was evaluated in an MPE mouse model. Mice received intrapleural PTS (165, 123.75, 82.5 mg/kg) or intraperitoneal CCL2 antibody (50 mg/kg) on days 4, 7, and 10. To validate clinical efficacy of PTS, a single-arm compassionate study was conducted in seven lung cancer patients with MPE. PTS was administered intrapleurally three times weekly, with doses increasing from 5 mL to 10 mL (330 mg/mL). Pleural effusion was assessed via B-ultrasound or CT. Treatment efficacy followed WHO standards: complete remission (CR) required total effusion resolution for over four weeks; partial remission (PR) indicated > 50% reduction without drainage; Stable disease (SD) refers to effusion decreasing by less than half, increasing by no more than a quarter, or remaining unchanged; progressive disease (PD) involved increased effusion requiring intervention. Overall remission rate (ORR) was determined by the sum of CR and PR, whereas MPE disease control rate (DCR) includes CR, PR, and SD combined. Results: In MPE animal model, the results showed that PTS significantly reduced MPE volume, and pleural tumor weight compared to the control group (p < 0.01). No pleural adhesion was observed in these mice. The single-arm exploratory study, which used PTS to treat MPE in lung cancer patients, enrolled seven subjects who completed three administrations of PTS. The results showed that the average volume of drained pleural effusion was significantly reduced from 1,163 mL at baseline to 300 mL 30 days after the last dosage (p < 0.05). By the end of PTS treatment, five subjects achieved CR, one had PR, one had SD, and no subject had PD. MPE ORR was 85.7% (6/7) and MPE DCR was 100% (7/7). Median time to reintervention for MPE was 94 days. No serious adverse reactions were observed. No patient had pleural or chest wall adhesions. These results suggest that PTS could both inhibit tumor growth and reduce MPE accumulation. Conclusions: PTS was demonstrated to be safe and effective when administered directly into the pleural cavity for MPE management. Intrapleural PTS administration shows potential in providing patients with MPE an alternative approach to chemotherapy or pleurodesis to alleviate their symptoms and more efficiently reduce their cancer burden. Further comprehensive studies are warranted to gain a better understanding of PTS in MPE treatment.