743P - Percutaneous Hepatic Perfusion (Chemosat® or CS-PHP) of Melphalan in Patients (PTS) with Hepatic Metastases from Melanoma: Phase III Pharmacokinetic Analysis

Abstract

ABSTRACT Background CS-PHP (CHEMOSAT®; Delcath Systems Inc, New York, NY) is a regional therapy which: i) isolates the liver using a system of percutaneously positioned catheters; ii) delivers high-dose chemotherapy directly into the hepatic artery; and iii) minimizes systemic toxicity by hemofiltration of hepatic venous blood. Methods A randomized phase III study compared CS-PHP delivery melphalan with best alternative care in pts with liver metastases from melanoma. A pharmacokinetic analysis was performed in a subset of pts from this study. Pts received melphalan 3.0 mg/kg ideal body weight via CS-PHP over 30 min with 60 min of hemofiltration starting at the time of perfusion. Blood samples (7 mL) were collected during cycle 1. Sample collection sites: arterial line; prefilter (extracorporeal circuit); postfilter (extracorporeal circuit). Sampling times: baseline; mid-infusion; immediate post-infusion; 5, 10, 15, 30 min post-infusion. Melphalan plasma concentrations were determined by HPLC with UV detection. Data were analyzed using a non-compartmental approach. Pharmacokinetic parameters: maximum plasma concentration (Cmax); area under concentration-time curve from t0 to final sample (AUClast); filter efficiency [(pre-filter AUClast) minus (post-filter AUClast) divided by (pre-filter AUClast)]. Results Plasma samples were available from 48 pts, of which 40 were evaluable. Mean absolute melphalan dose was 191mg (range 137-220mg) and duration of perfusion was 30 min (range 16-52 min). Mean filter extraction efficiency was 71.2% ± 10.4%. Filter efficiency did not change significantly with absolute melphalan dose (p = 0.86, Spearman) or rate of perfusion (p = 0.064, Spearman). Conclusions CS-PHP exposes the liver to high concentrations of melphalan. Filter extraction efficiency is consistent among pts and does not appear to be influenced by melphalan dose or rate of perfusion. Table: 743P Sample site N Cmax (ng/mL) AUClast (min.ng/mL) mean range mean range Prefilter 40 8728 4026-14,367 264,652 143,441-470,501 Postfilter 40 2330 930-4292 74,146 27,333-154,049 Systemic 37 1429 701-3203 50,777 25,566-111,362 Disclosure D.S. Johnston: Employee of Delcath Systems Inc. Stock ownership in Delcath. All other authors have declared no conflicts of interest.