A multicenter randomized controlled trial of intrapleural perfusion of methotrexate‐loaded tumor cell‐derived microparticles combined with systemic therapy for malignant pleural effusion

Abstract This study evaluated the efficacy and safety of intrapleural perfusion with methotrexate‐loaded tumor cell‐derived microparticles (MTX‐TMPs) combined with systemic therapy (ST) in patients with malignant pleural effusion (MPE) secondary to lung or breast cancer. In this multicenter, randomized, open‐label trial, 102 patients were assigned 1:1 to receive either MTX‐TMPs intrapleural perfusion (50 mL daily for 4 days) plus ST (cohort 1) or interleukin‐2 (IL‐2) intrapleural perfusion (50 mL every 3 days for three sessions) plus ST (cohort 2). The objective response rate (ORR) and disease control rate (DCR) of pleural effusion were evaluated in 91 patients (50 in cohort 1, 41 in cohort 2). ORR was significantly higher in cohort 1 than in cohort 2 (76.0% vs. 53.7%, p = 0.025), as was DCR (92.0% vs. 70.7%, p = 0.012). Among 83 patients included in the survival analysis, the median overall survival (OS) was 15.0 months (95% CI: 9.2–26.9) in cohort 1 and 6.9 months (95% CI: 5.3–15.8) in cohort 2 (HR = 0.75; 95% CI: 0.46–1.24; p = 0.266). One‐, two‐, and three‐year OS rates in cohort 1 were 55.3%, 36.2%, and 25.5%, compared to 38.9%, 25.0%, and 25.0% in cohort 2. Both regimens showed manageable safety profiles, with anemia, pyrexia, fatigue, leukopenia, gastrointestinal symptoms, and liver dysfunction being the most common treatment‐related adverse events. These findings suggest that intrapleural perfusion of MTX‐TMPs combined with ST represents a promising and safe strategy for the management of MPE in patients with lung or breast cancer.