1141P - Percutaneous hepatic perfusion (chemosat or cs-php) of melphalan vs. Best alternative care (BAC) in patients (pts) with hepatic metastases from mela...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Cytotoxic agents
Skin cancers
Therapy
Biological therapy
Presenter H. Alexander Jr.
Authors H.R. Alexander Jr.1, -. On Behalf Of Phase 3 Principal Investigators2
  • 1Surgery, University of Maryland Medical Center, Baltimore/US
  • 2-, -, Baltimore/US

Abstract

Background

CS-PHP (CHEMOSAT®; Delcath Systems Inc, New York, NY) is a regional therapy which isolates and perfuses the liver with high-dose chemotherapy. Unwanted systemic exposure is minimized by extracorporeal filtration of hepatic venous blood.

Methods

A prospective randomized multicenter phase 3 study compared CS-PHP of melphalan with BAC in pts with proven unresectable hepatic metastases from ocular or cutaneous melanoma. A survival update was performed on 31 March 2011. CS-PHP melphalan 3.0 mg/kg ideal body weight was infused into the hepatic artery over 30 min with concurrent extracorporeal filtration for 60 min. Up to 6 treatments were given every 4–8 wks. In the BAC group, crossover to CS-PHP melphalan was permitted after hepatic disease progression. The primary endpoint was investigator-assessed hepatic progression-free survival (hPFS). An exploratory post-hoc analysis of pts who crossed from BAC to CS-PHP vs. BAC-only pts was also performed.

Results

93 pts were randomized to CS-PHP (n = 44) or BAC (n = 49). After hepatic disease progression, 28 pts crossed over to CS-PHP. Results are shown in the Table. The most common grade 3/4 toxicities in CS-PHP pts (n = 40) were hematological peri-procedural thrombocytopenia (73%) and anemia (55%) and post-procedural (beyond day 4 post-treatment) neutropenia (93%) or thrombocytopenia (83%). The safety profile in crossover pts was similar to that in pts randomized to CS-PHP melphalan.

Conclusions

CS-PHP melphalan significantly prolonged hPFS compared with BAC in pts with liver-dominant metastatic melanoma, thereby meeting the primary study objective. Efficacy was similar after hepatic disease progression in BAC-CS-PHP crossover pts as in those randomized initially to CS-PHP.

Treatment group n Median hPFS, mo Hazard ratio (95% CI) Median OS, mo Hazard ratio (95% CI)
CS-PHP 44 8.0 0.35 (0.23-0.54)P < 0.0001 9.8 1.08 (0.69-1.68)NS
BAC 49 1.6 9.9
BAC only 21 1.6 0.32 4.1 0.33
BAC → CS-PHP crossover 28 8.8 15.3

Disclosure

All authors have declared no conflicts of interest.