Evaluation of Delcath Systems’ Generation 2 (GEN 2) Melphalan Hemofiltration System in a Porcine Model of Percutaneous Hepatic Perfusion

Abstract

PurposeA new melphalan hemoperfusion filter (GEN 2) was evaluated in a simulated-use porcine model of percutaneous hepatic perfusion (PHP). The current study evaluated melphalan filtration efficiency, the transfilter pressure gradient, and the removal of specific blood products.Materials and MethodsA porcine PHP procedure using the GEN 2 filter was performed under Good Laboratory Practice conditions to model the 60-min clinical PHP procedure.ResultsThe mean filter efficiency for removing melphalan in six filters was 99.0 ± 0.4 %. The transfilter pressure gradient across the filter averaged 20.9 mmHg for the 60-min procedure. Many blood components, including albumin and platelets, decreased on average from 3.55 to 2.02 g/dL and from 342 to 177 × 10.e3/μL, respectively, during the procedure.ConclusionThe increased melphalan extraction efficiency of the new filter is expected to decrease systemic melphalan exposure. In addition, the low transfilter pressure gradient resulted in low resistance to blood flow in the GEN 2 filter, and the changes to blood components are expected to be clinically manageable.Electronic supplementary materialThe online version of this article (doi:10.1007/s00270-013-0826-5) contains supplementary material, which is available to authorized users.

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

“…The mean filtration rate in our study was lower than that obtained in in vivo, pre-clinical studies. In a study including 6 pigs treated with PHP with the first-generation filter, the filter extraction rate was 99% [ 10 ]. In our study, the mean efficiency dropped from 95.4% at T 10 to 77.5% at T end infusion , although the difference did not reach statistical significance.…”

“…In our study, the mean efficiency dropped from 95.4% at T 10 to 77.5% at T end infusion , although the difference did not reach statistical significance. Pre-clinical studies have also shown that the filter efficiency decreases during the perfusion [ 10 ]. We hypothesise that the filter is more saturated at the end of the procedure.…”

“…The activated carbon particles have been changed in shape (from granular to spherical), density (from 0.600 to 0.560 to 0.195–0.185 g/ml), size (mean ± standard deviation from 1363 ± 457 to 720 ± 102 μm), and volume per cartridge (from 500 to 550 ml). In a porcine study, the extraction rate of the GEN 2 filter was 99 ± 0.4% [ 10 ]. Initial clinical experiences seem to indicate that the use of the GEN 2 filter may indeed reduce systemic toxicity [ 7 ].…”

Percutaneous hepatic perfusion with melphalan for unresectable liver metastasis

“…Some fatalities were observed on this trial and each death lead to further safety maneuvers in the development of improved filters. [15,16] The authors concluded that the results of their phase III study demonstrate the efficacy of PHP-Mel. They report that the toxicity is significant but manageable in order to provide effective therapy for this select cohort of patients.…”

“…These filters are reported to have increased melphalan extraction efficiency. [15] In the portion of patients treated with the second generation filters, the toxicity was found to be milder and patients experienced a faster recovery. [14] Similar to other groups with experience in PHP, Vogl et al [14] concluded that PHP for non-resectable liver metastasis is a feasible treatment.…”