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原发性和继发性恶性肿瘤的肺灌注优化:I期安全性和药物递送数据的初步分析

Pulmonary Suffusion Refinements for Primary and Secondary Malignancies: Preliminary Analyses of Phase I Safety and Drug Delivery Data.

作者信息

Demmy Todd, Abdelhady Samah, Tomaszewski Garin, Petroziello Michael, Hasan Omar, Hennon Mark, Dexter Elisabeth, Vadehra Deepak, Gupta Ajay, Grand'Maison Anne, Dy Grace, Yendamuri Sai

机构信息

Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA.

Department of Pediatric Hematology and Oncology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Strs., Buffalo, NY 14263, USA.

出版信息

Cancers (Basel). 2025 Sep 2;17(17):2880. doi: 10.3390/cancers17172880.

Abstract

: We sought to document interim methodologic improvements and preliminary results for pulmonary suffusion. : A Phase I/II trial of thoracoscopic lung suffusion for resectable sarcoma and colorectal carcinoma metastases followed a pilot study on oligometastatic lung malignancy at a comprehensive cancer center. Primary-specific chemotherapy doses (cisplatin, oxaliplatin, doxorubicin, or gemcitabine) suffused unilaterally for 30 min were escalated to amplify regional deliveries three-fold. Drug delivery was measured with tissue, blood samples, and Tc; pulmonary function tests and clinical adverse events (AEs) assessed safety and tolerance. : From 2008-2025, 31 ECOG 0-2 patients (10 male) aged 33-75 years had unilateral lung suffusion (16 right, 14 left, 1 aborted, and 8 sides selected randomly). Vascular occlusion intolerance was immediate or delayed (25 min) in two cases. Two catheter-positioning grade 3 AEs occurred: hypotension with troponin leak (1) and atrial fibrillation (1). Patients averaged 1.3 ± 1.2 metastasectomies (17 sub-lobar, 8 lobar resections, and 2 intentional open cytoreductive metastasectomies). Hospitalizations were brief (1-4 days) except for 6-7 day stays in the only two open cases and one doxorubicin (grade 4 hypoxic respiratory failure) case. Ninety-day survival was 100%, and the Phase I delivery goal of 12.75 mg/m 65 (15% systemic) was achieved for oxaliplatin. Lung function was preserved according to Tc differentials within 6.1 ± 7.1% of the predicted reductions at 30 days. Sampling delays, tracer discordances, and atypical pharmacokinetics reduced tissue drug detections. Recent pulmonary artery snaring cases (two) demonstrated in-flow control more stable than that of balloon occlusions. : Suffusion for metastatic malignancies appears safe and warrants further investigation.

摘要

我们试图记录肺灌注的中期方法改进和初步结果。一项针对可切除肉瘤和结直肠癌转移灶的胸腔镜肺灌注I/II期试验,是在一家综合癌症中心对寡转移性肺恶性肿瘤的初步研究之后进行的。将单侧灌注30分钟的原发特异性化疗剂量(顺铂、奥沙利铂、阿霉素或吉西他滨)逐步增加,以使区域给药量增加三倍。通过组织、血液样本和锝测量药物递送情况;通过肺功能测试和临床不良事件(AE)评估安全性和耐受性。2008年至2025年期间,31例ECOG 0-2级患者(10例男性),年龄在33至75岁之间,接受了单侧肺灌注(16例右侧,14例左侧,1例中止,8例随机选择一侧)。两例出现血管闭塞不耐受,表现为即刻或延迟(25分钟)。发生了两例3级导管定位不良事件:一例伴有肌钙蛋白泄漏的低血压和一例房颤。患者平均进行了1.3±1.2次转移灶切除术(17例亚肺叶切除、8例肺叶切除和2例有意的开放性细胞减灭性转移灶切除术)。除了仅有的两例开放性手术和一例阿霉素(4级低氧性呼吸衰竭)病例住院6至7天外,其余住院时间较短(1至4天)。90天生存率为100%,奥沙利铂达到了12.75mg/m²(15%全身暴露)的I期给药目标。根据锝差异,肺功能在30天时保持在预测降低值的6.1±7.1%以内。采样延迟、示踪剂不一致和非典型药代动力学降低了组织药物检测率。最近的两例肺动脉圈套病例显示,入流控制比球囊闭塞更稳定。转移性恶性肿瘤的灌注似乎是安全的,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2254/12427383/7005c43c6b77/cancers-17-02880-g001.jpg

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