AUTHOR=Dong Xiaorong , Huang Yu , Yi Tienan , Hu Chunhong , Gao Quanli , Chen Yuan , Zhang Jing , Chen Jianhua , Liu Li , Meng Rui , Zhang Sheng , Dai Xiaofang , Fei Shihong , Jin Yang , Yin Ping , Hu Yanping , Wu Gang 

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 study

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1002938

DOI=10.3389/fimmu.2022.1002938

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><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).</p></sec><sec><title>Methods</title><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<sup>2</sup> d1) and cisplatin (75 mg/m<sup>2</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.</p></sec><sec><title>Results</title><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%, <italic>P</italic> = 0.0237). The ORR of target lesions was 25.64% in group A and 20.51% in group B (<italic>P</italic> = 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% CI, 6.1-10.4) months in group B (<italic>P</italic> = 0.6893), and median OS were 19.9 (95% CI, 17.1-28.5) months and 17.5 (95% CI, 11.6-25.0) months (<italic>P</italic> = 0.4500), 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.</p></sec><sec><title>Conclusion</title><p>Intrapleural infusion of TMPs-MTX combined with pemetrexed-cisplatin chemotherapy is safe and effective against MPE in patients with advanced non-squamous NSCLC.</p></sec><sec><title>Clinical trial registration</title><p><uri xlink:href="http://www.chictr.org.cn" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.chictr.org.cn</uri> (ChiCTR-ICR-15006304).</p></sec>