Minimally invasive intra-arterial regional therapy for metastatic melanoma: isolated limb infusion and percutaneous hepatic perfusion

Abstract

Introduction: In-transit melanoma or melanoma presenting as unresectable liver metastases are clinical situations with limited therapeutic options. Regional intra-arterial therapies provide efficacious treatment alternatives for these patients. Through surgical techniques of vascular isolation, regional therapies deliver high-dose chemotherapy to tumor cells while minimizing systemic exposure. However, percutaneous techniques such as isolated limb infusion (ILI) and percutaneous hepatic perfusion (PHP) have been developed, which provide a minimally invasive means of obtaining vascular isolation of target organs.

Areas covered: Areas covered in this review include the techniques of ILI and PHP, the chemotherapeutic agents utilized during these regional therapies and the clinical responses seen after ILI and PHP. The pharmacokinetics of regional chemotherapy utilized during ILI and PHP is also reviewed with an additional focus on novel ways to optimize drug delivery to improve response rates and attempts to define the potential systemic manifestations of regional therapeutics.

Expert opinion: Unresectable hepatic and limb in-transit metastases from melanoma are very difficult to treat. Systemic chemotherapy has largely been ineffective. Both the minimally invasive, percutaneous techniques of ILI and PHP are excellent methods used to deliver extremely high-dose chemotherapy regionally to patients harboring metastatic melanoma confined to an extremity or liver, respectively. Studies, from prospectively maintained databases as well as Phase II and III trials, have shown the great efficacy of these techniques.

Figure 1. Percutaneous hepatic perfusion circuit

The Delcath catheter is a 16 Fr polyethylene multi-lumen catheter that permits occlusion of the IVC proximal and distal to the hepatic veins and allows for vascular isolation of the liver. The Delcath catheter is percutaneously introduced into the IVC and fluoroscopically positioned. The catheter is attached to the extracorporeal circuit consisting of a centrifugal pump and drug filtration cartridges. The proximal and distal balloons are inflated and high-dose chemotherapy is then infused into the liver via a catheter in the hepatic artery. The hepatic venous outflow is circulated into the pump and subsequently into two activated carbon filtration cartridges that are connected in parallel. The filtered blood is then returned to the systemic circulation through a catheter in either the internal jugular or subclavian veins. This is an original image with copyright belonging to Delcath Systems, Inc. Reproduced with permission from Delcath Systems, Inc. IVC: Inferior vena cava.