Percutaneous hepatic perfusion with melphalan for unresectable liver metastasis

Abstract

Percutaneous hepatic perfusion (PHP) is an investigative technique for treating patients with diffuse unresectable metastatic liver disease. The technique has been clinically evaluated and shows great treatment potential for regional therapy to the liver. The advantage of PHP lies in its minimally invasive approach and ability to be repeated when compared to isolated hepatic perfusion. In a literature search, 135 publications were screened and 16 of these publications, including clinical trials and reviews, contributed to this review of PHP with melphalan. Melphalan is an alkylating agent that, when used as the chemotherapeutic agent in PHP, has shown potential for significant control of tumor burden in the liver, especially in metastatic ocular melanoma. In the current landscape of liver directed therapy, PHP is a viable option for those with unresectable metastatic disease to the liver. This article will focus on the technical aspects of PHP and describe the current data available from clinical trials, including outcomes of patients treated with this minimally invasive approach.

Keywords

Percutaneous hepatic perfusion / melphalan / unresectable liver metastasis / metastatic melanoma to the liver / ocular melanoma

References

[1] Ruers T.Treatment of liver metastases, an update on the possibilities and results..Eur J Cancer2002;38:1023-33

[2] Reddy SK,Alexander HRJr.Isolated hepatic perfusion for patients with liver metastases..Ther Adv Med Oncol2014;6:180-94 PMCID:PMC4107710

[3] Alexander HRJr.Development of isolated hepatic perfusion via the operative and percutaneous techniques for patients with isolated and unresectable liver metastases..Cancer J2010;16:132-41

[4] Magge D,Zeh HJ3rd,Steel J,Jones HL,Bartlett DL.Outcome analysis of a decade-long experience of isolated hepatic perfusion for unresectable liver metastases at a single institution..Ann Surg2014;259:953-9

[5] Lienard D,Delmotte JJ,Lejeune FJ.High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma..J Clin Oncol1992;10:52-60

[6] Ravikumar TS,Bodden W,Strair R,Hendler R,D'Andrea E.Percutaneous hepatic vein isolation and high-dose hepatic arterial infusion chemotherapy for unresectable liver tumors..J Clin Oncol1994;12:2723-36

[7] Curley SA,Dougherty TB,Stone DL,Guercio S,Carrasco CH,Hohn DC.Complete hepatic venous isolation and extracorporeal chemofiltration as treatment for human hepatocellular carcinoma: a phase I study..Ann Surg Oncol1994;1:389-99

[8] Pingpank JF,Chang R,Neeman Z,Figg WD,Beresneva T,Alexander HR.Phase I study of hepatic arterial melphalan infusion and hepatic venous hemofiltration using percutaneously placed catheters in patients with unresectable hepatic malignancies..J Clin Oncol2005;23:3465-74 PMCID:PMC2374756

[9] Pingpank JF,Alexander HR,Zager JS,Whitman ED,Siskin GP.A phase III random assignment trial comparing percutaneous hepatic perfusion with melphalan (PHP-mel) to standard of care for patients with hepatic metastases from metastatic ocular or cutaneous melanoma..J Clin Oncol2010;28 suppl:LBA8512

[10] Minor DR,Alberts D,Tardelli G.A clinical and pharmacokinetic study of isolated limb perfusion with heat and melphalan for melanoma..Cancer1985;55:2638-44

[11] Parsons PG,Morrison L.Mechanism of melphalan resistance developed in vitro in human melanoma cells..Cancer Res1981;41:1525-34

[12] Miao N,Alexander HR,Beresneva T.Percutaneous hepatic perfusion in patients with metastatic liver cancer: anesthetic, hemodynamic, and metabolic considerations..Ann Surg Oncol2008;15:815-23

[13] Forster MR,Perez MC,Chaudhry T.Chemosaturation with percutaneous hepatic perfusion for unresectable metastatic melanoma or sarcoma to the liver: a single institution experience..J Surg Oncol2014;109:434-9 PMCID:PMC4503311

[14] Vogl TJ,Scholtz JE,Paetzold S,Orsi F,Ferrucci P.Chemosaturation with percutaneous hepatic perfusions of melphalan for hepatic metastases: experience from two European centers..Rofo2014;186:937-44

[15] Moeslein FM,Appling WM,Jarvis KD,Sheets TP,Johnston DS.Evaluation of Delcath Systems' Generation 2 (GEN 2) melphalan hemofiltration system in a porcine model of percutaneous hepatic perfusion. Cardiovasc.Intervent Radiol2014;37:763-9 PMCID:PMC4024156

[16] Hughes MS,Faries M,Royal RE,Choi J,Whitman E,Siskin G,Toomey MA,Beresnev T.Results of a randomized controlled multicenter phase III trial of percutaneous hepatic perfusion compared with best available care for patients with melanoma liver metastases..Ann Surg Oncol2016;23:1309-19

[17] Niederkorn JY.Immune escape mechanisms of intraocular tumors..Prog Retin Eye Res2009;28:329-47 PMCID:PMC2727063