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.

Regional therapy in metastatic melanoma: an update on minimally invasive intraarterial isolated limb infusion and percutaneous hepatic perfusion

“…The vascular anatomy of the extremities and the liver are particularly amenable to isolation and intraarterial regional perfusion-based therapy with much less morbidity than surgical isolation of the other mentioned anatomic sites disease does potentially offer a benefit for certain patients with metastatic melanoma because a subgroup will not develop distant metastasis despite a high burden of regional disease. The 5-year survival rates for patients with cutaneous in-transit and distant metastases range from 30 to 50% in patients with stage IIIb or IIIc disease, and < 20% in patients with stage IV disease [8][9][10][11]. Accomplishing control of in-transit disease (stage IIIb/c) has demonstrated improved survival in select cases (25 --30% 15-year survival) [8].…”

“…The 5-year survival rates for patients with cutaneous in-transit and distant metastases range from 30 to 50% in patients with stage IIIb or IIIc disease, and < 20% in patients with stage IV disease [8][9][10][11]. Accomplishing control of in-transit disease (stage IIIb/c) has demonstrated improved survival in select cases (25 --30% 15-year survival) [8].…”

“…Uveal melanoma is the most common primary malignant neoplasm of the eye with over half of these patients eventually developing distant metastasis. Interestingly, 80% of those patients who develop metastatic disease have the liver as the only site of metastatic spread [8,9]. Accordingly, it provides a scenario for liver-directed regional therapy in select cases.…”

“…Accordingly, it provides a scenario for liver-directed regional therapy in select cases. One-year survival for patients with uveal melanoma with and liver metastasis is 10 --15%, with < 9-months median overall survival [8][9][10][11]. Further more, systemic therapy has demonstrated little efficacy, as trials utilizing chemotherapy produced only 5 --20% response rates [8][9][10][11].…”

“…One-year survival for patients with uveal melanoma with and liver metastasis is 10 --15%, with < 9-months median overall survival [8][9][10][11]. Further more, systemic therapy has demonstrated little efficacy, as trials utilizing chemotherapy produced only 5 --20% response rates [8][9][10][11]. This review provides a comprehensive overview of all current data on isolated limb infusion (ILI) and percutaneous hepatic perfusion (PHP), including evidence on the pharmacokinetics (PK) of regional chemotherapy.…”