Intrapleural infusion of tumor cell-derived microparticles packaging methotrexate or saline combined with pemetrexed-cisplatin chemotherapy for the treatment of malignant pleural effusion in advanced non-squamous non-small cell lung cancer: A double-blind, randomized, placebo-controlled study

作者：Xiaorong Dong, Yu Huang, Tienan Yi, Chunhong Hu, Quanli Gao, Yuan Chen, Jing Zhang, Jianhua Chen, Li Liu, Rui Meng, Sheng Zhang, Xiaofang Dai, Shihong Fei, Yang Jin, Ping Yin, Yanping Hu, Gang Wu · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.1002938 · 被引用次数：17 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Pleural and Pulmonary Diseases、Extracellular vesicles in disease

Background Preclincal studies showed the promising efficacy of tumor cell-derived microparticles packaging methotrexate (TMPs-MTX) to treat advanced non-squamous non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE). Methods This randomized, double-blind, placebo-controlled study was conducted at six hospitals in China from 20 July 2015 to 25 April 2019. Patients newly diagnosed with non-squamous NSCLC with MPE were randomly assigned to receive TMPs-MTX (group A) or saline (group B). Patients in both groups received pemetrexed (500 mg/m 2 d1) and cisplatin (75 mg/m 2 in total for d1-d2). Intrapleural infusion (50 mL saline containing 5 units of TMPs-MTX per perfusion, once every 48 hours, six total perfusions) was initiated on day 5 after pemetrexed-cisplatin chemotherapy. The primary outcome was the objective response rate (ORR) of MPE. Secondary outcomes included the ORR of target lesions, progression-free survival (PFS), overall survival (OS), toxicity, and pleural fluid properties. Results A total of 86 patients were enrolled in this study and randomly assigned to either group A or group B. Of these, 79 patients were evaluable for response. The ORR of MPE in group A was significantly higher than that in group B (82.50% vs. 58.97%, P = 0.0237). The ORR of target lesions was 25.64% in group A and 20.51% in group B ( P = 0.5909), respectively. With a median follow-up time of 18.8 months, median PFS were 6.4 (95% CI, 4.5-12.3) months in group A and 7.3 (95%...