دورية أكاديمية
Safety and feasibility of ultrasound-triggered targeted drug delivery of doxorubicin from thermosensitive liposomes in liver tumours (TARDOX): a single-centre, open-label, phase 1 trial
| العنوان: | Safety and feasibility of ultrasound-triggered targeted drug delivery of doxorubicin from thermosensitive liposomes in liver tumours (TARDOX): a single-centre, open-label, phase 1 trial |
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| المؤلفون: | Lyon, PC, Gray, MD, Mannaris, C, Folkes, LK, Stratford, M, Campo, L, Chung, DYF, Scott, S, Anderson, M, Goldin, R, Carlisle, R, Wu, F, Middleton, MR, Gleeson, FV, Coussios, CC |
| المصدر: | 1039 ; 1027 |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2018 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Oncology, INTENSITY FOCUSED ULTRASOUND, RABBIT VX2 TUMORS, RADIOFREQUENCY ABLATION, RESPONSE CRITERIA, SOLID TUMORS, HYPERTHERMIA, CANCER, MICROENVIRONMENT, RESISTANCE, RECIST, Aged, Antibiotics, Antineoplastic, Doxorubicin, Drug Delivery Systems, Female, Humans, Induced, Liver Neoplasms, Male, Middle Aged, Polyethylene Glycols, Ultrasonography, Oncology & Carcinogenesis, 1112 Oncology and Carcinogenesis |
| جغرافية الموضوع: | England |
| الوصف: | BACKGROUND: Previous preclinical research has shown that extracorporeal devices can be used to enhance the delivery and distribution of systemically administered anticancer drugs, resulting in increased intratumoural concentrations. We aimed to assess the safety and feasibility of targeted release and enhanced delivery of doxorubicin to solid tumours from thermosensitive liposomes triggered by mild hyperthermia, induced non-invasively by focused ultrasound. METHODS: We did an open-label, single-centre, phase 1 trial in a single UK hospital. Adult patients (aged ≥18 years) with unresectable and non-ablatable primary or secondary liver tumours of any histological subtype were considered for the study. Patients received a single intravenous infusion (50 mg/m2) of lyso-thermosensitive liposomal doxorubicin (LTLD), followed by extracorporeal focused ultrasound exposure of a single target liver tumour. The trial had two parts: in part I, patients had a real-time thermometry device implanted intratumourally, whereas patients in part II proceeded without thermometry and we used a patient-specific model to predict optimal exposure parameters. We assessed tumour biopsies obtained before and after focused ultrasound exposure for doxorubicin concentration and distribution. The primary endpoint was at least a doubling of total intratumoural doxorubicin concentration in at least half of the patients treated, on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02181075, and is now closed to recruitment. FINDINGS: Between March 13, 2015, and March 27, 2017, ten patients were enrolled in the study (six patients in part I and four in part II), and received a dose of LTLD followed by focused ultrasound exposure. The treatment resulted in an average increase of 3·7 times in intratumoural biopsy doxorubicin concentrations, from an estimate of 2·34 μg/g (SD 0·93) immediately after drug infusion to 8·56 μg/g (5·69) after focused ultrasound. Increases of two to ten times were observed in seven ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1470-2045 |
| العلاقة: | Lancet Oncology; http://hdl.handle.net/10044/1/61544Test |
| DOI: | 10.1016/S1470-2045(18)30332-2 |
| الإتاحة: | https://doi.org/10.1016/S1470-2045Test(18)30332-2 http://hdl.handle.net/10044/1/61544Test |
| حقوق: | © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4·0 license (https://creativecommons.org/licenses/by/4.0Test/) |
| رقم الانضمام: | edsbas.4BA61745 |
| قاعدة البيانات: | BASE |
| تدمد: | 14702045 |
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| DOI: | 10.1016/S1470-2045(18)30332-2 |