Percutaneous hepatic perfusion with melphalan in uveal melanoma: A safe and effective treatment modality in an orphan disease

Abstract

BackgroundMetastatic uveal melanoma (UM) carries a poor prognosis; liver is the most frequent and often solitary site of recurrence. Available systemic treatments have not improved outcomes. Melphalan percutaneous hepatic perfusion (M‐PHP) allows selective intrahepatic delivery of high dose cytotoxic chemotherapy.MethodsRetrospective analysis of outcomes data of UM patients receiving M‐PHP at two institutions was performed. Tumor response and toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) v4.03, respectively.ResultsA total of 51 patients received 134 M‐PHP procedures (median of 2 M‐PHPs). 25 (49%) achieved a partial (N = 22, 43.1%) or complete hepatic response (N = 3, 5.9%). In 17 (33.3%) additional patients, the disease stabilized for at least 3 months, for a hepatic disease control rate of 82.4%. After median follow‐up of 367 days, median overall progression free (PFS) and hepatic progression free survival (hPFS) was 8.1 and 9.1 months, respectively and median overall survival was 15.3 months. There were no treatment related fatalities. Non‐hematologic grade 3‐4 events were seen in 19 (37.5%) patients and were mainly coagulopathic (N = 8) and cardiovascular (N = 9).ConclusionsM‐PHP results in durable intrahepatic disease control and can form the basis for an integrated multimodality treatment approach in appropriately selected UM patients.

Recent Breakthroughs in Metastatic Uveal Melanoma: A Cause for Optimism?

“…An initial randomized Phase III study completed several years ago and showed an improvement in hepatic PFS (7.0 vs 1.6 months; p < 0.0001) when compared with investigators' choice, however no improvement in overall survival was observed (10.6 vs 10.0 months; p = 0.77), although this may have been partly due to patient crossover [16]. More recently, a case series combining data from two major centers reported a median overall survival of 15 months in 51 patients [17]. These results, while encouraging, require confirmation in a randomized study and an international Phase III (FOCUS, NCT026786572) comparing percutaneous hepatic perfusion with investigator choice is currently enrolling patients.…”

Safety of Percutaneous Hepatic Perfusion with Melphalan in Patients with Unresectable Liver Metastases from Ocular Melanoma Using the Delcath Systems’ Second-Generation Hemofiltration System: A Prospective Non-randomized Phase II Trial

“…Although survival results are still pending, it is of clinical relevance to share the results on safety and toxicity in advance. The aim of this paper was to report all safety and toxicity results and compare these with historical data from studies on M-PHP using the first-generation filter [ 1 , 6 , 8 , 11 , 12 ]. Our data on the efficacy of M-PHP with the GEN 2 filter will be reported separately.…”

Chemoreduction of Orbital Recurrence of Uveal Melanoma by Intra-Arterial Melphalan

“…This may raise concern for an increased risk of myelosuppression in the latter technique. However, "most" patients treated with isolated limb perfusion received granulocyte colony-stimulating factor [9]. On the contrary, our single patient did not have evidence of myelosuppression.…”

“…The drug choice of melphalan is grounded in clinical responses noted in the treatment of cutaneous melanoma by isolated limb perfusion and liver metastases of uveal melanoma by isolated hepatic perfusion [5,6,9]. Preclinical data support the therapeutic response of human melanoma lines to melphalan and have shown an enhanced response with hyperthermia [20,21].…”

“…It consists of localized delivery of cytotoxic melphalan to the site of disease, without exposing vital organs to the consequences of these high doses. A similar technique, percutaneous isolated hepatic perfusion, involves a similar technique of melphalan delivery and has established a hepatic control rate for uveal melanoma of 82.4% [7][8][9]. Our group has extensive experience in applying this rationale to the treatment of retinoblastoma through the technique of ophthalmic artery chemosurgery [10].…”