Isolated hepatic perfusion for patients with liver metastases

Abstract

Up to 80% of colorectal, melanoma, and neuroendocrine liver metastases are unresectable due to excessive tumor burden. Isolated hepatic perfusion (IHP) administers intensive therapy to the liver while limiting systemic toxicity and thus may have an important role in the management of unresectable liver metastases. This review s describes the development of IHP, initial clinical results, open and percutaneous IHP techniques, and contemporary long-term treatment outcomes. IHP with melphalan or tumor necrosis factor α (TNFα) has been shown to achieve hepatic response rates of greater than 50% with progression-free survival of greater than 12 months among patients with refractory ocular melanoma liver metastases. The only series describing outcomes of IHP for neuroendocrine liver metastases notes an overall response rate of 50% and a median actuarial overall survival of 48 months after IHP treatment with melphalan or TNFα. The majority of studies that have evaluated IHP have been performed in patients with colorectal cancer liver metastases (CRCLM). In aggregate, survival results from retrospective studies and phase I/II clinical trials suggest that IHP demonstrated no significant survival benefit compared with systemic chemotherapy alone as first-line therapy. In contrast, IHP does improve outcomes relative to that provided by second-line chemotherapy for CRCLM, with overall response rates of 60% and median duration of liver response of 12 months. Continued evaluation of IHP for unresectable liver metastases is necessary to establish its role in multidisciplinary treatment approaches.

Obstacles and future of gene therapy for hemophilia

“…In NHPs, both direct portal infusion after a blood-removing saline flush and fluoroscopically guided infusion with a microballoon catheter (which temporarily isolates the infusate) allowed for comparable levels of FIX transgene expression in animals with NAb titers between 1:14 and 1:56 as in animals without detectable NAbs [26]. Though certainly more invasive than systemic infusion, these techniques [27] and other localized perfusion techniques such as percutaneous hepatic perfusion [28] are likely translatable to patients. However, isolated muscle perfusion was unable to overcome high-titer NAbs to AAV2 (1:30, 1:300) due to previous vector administration in HB dogs, though the combined use of an AAV6 serotype vector and localized perfusion achieved FIX levels between 5 and 2% despite very high preexisting anti-AAV2 NAb titers of 1:100 and 1:1000, respectively [29].…”

Recent advances in uveal melanoma treatment

“…IHP with the alkylating agent melphalan or TNF‐α has shown to achieve hepatic RRs of greater than 50% with progression‐free survival (PFS) of more than 12 months in patients with refractory UM liver metastases. These results exceed the outcomes of those obtained with systemic chemotherapy . The EORTC 18021 phase III trial (NCT00110123) is another study where IHP was compared to intravenous systemic chemotherapy in patients with liver metastasis from UM.…”

In vivo Studies for Drug Development via Oral Delivery: Challenges, Animal Models and Techniques

“…Isolated hepatic perfusion is a surgical technique used for treatment of nonresectable liver cancer, liver metastases, and melanoma where systemic chemotherapy is the only other option. The isolation of the liver allows for a delivery of substantially higher doses of chemotherapy at elevated temperatures that would be lethal if administered by traditional systemic delivery [91,92]. These isolated organ perfusion techniques allow higher concentrations of chemotherapy to be delivered to the targeted organ while ensuring the vitality of other organs.…”