{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:27:54Z","timestamp":1793392074441,"version":"4.5.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T00:00:00Z","timestamp":1664928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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<jats:sup>2<\/jats:sup> d1) and cisplatin (75 mg\/m<jats:sup>2<\/jats:sup> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0237). The ORR of target lesions was 25.64% in group A and 20.51% in group B (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.5909), 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% CI, 6.1-10.4) months in group B (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.6893), and median OS were 19.9 (95% CI, 17.1-28.5) months and 17.5 (95% CI, 11.6-25.0) months (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.4500), respectively. The incidence rates of adverse events were similar in the two groups. The most common treatment-related adverse events were chemotherapy-induced toxicities, including fever, gastrointestinal reactions, hepatic dysfunction, and leukopenia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intrapleural infusion of TMPs-MTX combined with pemetrexed-cisplatin chemotherapy is safe and effective against MPE in patients with advanced non-squamous NSCLC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:uri>http:\/\/www.chictr.org.cn<\/jats:uri> (ChiCTR-ICR-15006304).<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.1002938","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T13:19:34Z","timestamp":1664975974000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["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 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