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Clinical Trial
. 2017 Aug;40(8):1196-1205.
doi: 10.1007/s00270-017-1630-4. Epub 2017 Apr 27.

Prospective Clinical and Pharmacological Evaluation of the Delcath System's Second-Generation (GEN2) Hemofiltration System in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan

Eleonora M de Leede  1 , Mark C Burgmans  2 , T Susanna Meijer  3 , Christian H Martini  4 , Fred G J Tijl  5 , Jaap Vuyk  4 , Arian R van Erkel  3 , Cornelis J H van der Velde  1 , Ellen Kapiteijn  6 , Alexander L Vahrmeijer  1
Affiliations
Clinical Trial

Prospective Clinical and Pharmacological Evaluation of the Delcath System's Second-Generation (GEN2) Hemofiltration System in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan

Eleonora M de Leede et al. Cardiovasc Intervent Radiol. 2017 Aug.

Erratum in

Abstract

Introduction: Percutaneous hepatic perfusion (PHP) with melphalan is an effective treatment for patients with hepatic metastases, but associated with high rates of bone marrow depression. To reduce systemic toxicity, improvements have been made to the filtration system. In pre-clinical studies, the Delcath System's GEN2 filter was superior to the first-generation filters. In this clinical study, we analysed the pharmacokinetics and toxicity of PHP using the new GEN2 filter.

Methods and materials: Starting February 2014, two prospective phase II studies were initiated in patients with hepatic metastases from ocular melanoma or colorectal cancer. In 10 PHP procedures performed in the first 7 enrolled patients, blood samples were obtained to determine filter efficiency and systemic drug exposure. PHP was performed with melphalan 3 mg/kg with a maximum of 220 mg. Complications were assessed according to CTCAE v4.03. Response was assessed according to RECIST 1.1.

Results: Pharmacokinetic analysis of blood samples showed an overall filter efficiency of 86% (range 71.1-95.5%). The mean filter efficiency decreased from 95.4% 10 min after the start of melphalan infusion to 77.5% at the end of the procedure (p = 0.051). Bone marrow depression was seen after up to 80.0% of 10 procedures, but was self-limiting and mostly asymptomatic. No hypotension-related complications or procedure-related mortality occurred.

Conclusion: The GEN2 filter has a higher melphalan filter efficiency compared to the first-generation filters and a more consistent performance. PHP with the GEN2 filter appears to have an acceptable safety profile, but this needs further validation in larger studies.

Keywords: Cancer; Chemoembolisation; Colorectal cancer; Interventional oncology; Liver; Uveal melanoma.

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Conflict of interest statement

Conflict of interest

Delcath Systems provided in-kind support and an educational grant for the conduct of the study. Three of the authors received travel fees to attend expert meetings sponsored by Delcath.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional and/or National Research Committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Schematic overview of PHP circuit. Indicated are the pharmacokinetic sampling points
Fig. 2
Fig. 2
Filter efficiency per patient at different time points during the procedure. The mean filter efficiency was calculated at three time points during the 10 procedures. First at ten minutes after the start of the melphalan infusion, then at the end of the melphalan infusion, and at the end of the washout period
Fig. 3
Fig. 3
Mean systemic concentration of melphalan of all patients over time. A mean concentration of systemic melphalan was calculated at different time points; for all ten procedures, the bars indicate the standard deviation (SD). The horizontal dotted line at 0.5 µg/ml indicates the detection limit of melphalan in plasma
See this image and copyright information in PMC

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