Metastatic uveal melanoma (UM) carries a poor prognosis; liver is the most frequent and often solitary site of recurrence.,Available systemic treatments have not improved outcomes.,Melphalan percutaneous hepatic perfusion (M‐PHP) allows selective intrahepatic delivery of high dose cytotoxic chemotherapy.,Retrospective analysis of outcomes data of UM patients receiving M‐PHP at two institutions was performed.,Tumor response and toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) v4.03, respectively.,A total of 51 patients received 134 M‐PHP procedures (median of 2 M‐PHPs). 25 (49%) achieved a partial (N = 22, 43.1%) or complete hepatic response (N = 3, 5.9%).,In 17 (33.3%) additional patients, the disease stabilized for at least 3 months, for a hepatic disease control rate of 82.4%.,After median follow‐up of 367 days, median overall progression free (PFS) and hepatic progression free survival (hPFS) was 8.1 and 9.1 months, respectively and median overall survival was 15.3 months.,There were no treatment related fatalities.,Non‐hematologic grade 3‐4 events were seen in 19 (37.5%) patients and were mainly coagulopathic (N = 8) and cardiovascular (N = 9).,M‐PHP results in durable intrahepatic disease control and can form the basis for an integrated multimodality treatment approach in appropriately selected UM patients.
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.,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.,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.,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.