Percutaneous Hepatic Perfusion with Melphalan in Patients with Unresectable Ocular Melanoma Metastases Confined to the Liver: A Prospective Phase II Study

Abstract

Background Ocular melanoma is the most common primary intraocular malignancy and has a very poor prognosis once liver metastases occur. The aim of this study was to prospectively assess the efficacy and safety of percutaneous hepatic perfusion with melphalan (M-PHP) using the new second-generation (GEN 2) hemofiltration system in patients with ocular melanoma metastases confined to the liver. Methods Prospective, single-center, single-arm, phase II study including patients with unresectable ocular melanoma metastases confined to the liver. Treatment consisted of two M-PHP procedures at 6–8 weeks interval. Procedures were performed using the CHEMOSAT (GEN 2) system with 3 mg/kg melphalan. Primary endpoints were overall response rate (ORR) and best overall response (BOR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), hepatic PFS (hPFS), and safety. Results Sixty-four M-PHP procedures were performed in 35 patients between February 2014 and June 2017. The ORR was 72%. BOR was as follows: complete response in 3%, partial response in 69%, stable disease in 13%, and progressive disease in 16%. There was no treatment-related mortality. Fourteen serious adverse events occurred. At a median follow-up of 19.1 months (range 5.6–69.5), median OS was 19.1 months and was significantly longer in responders than in nonresponders (27.5 vs. 11.9 months, p < 0.001). The 1- and 2-year OS was 77% and 43%, respectively. PFS and hPFS were 7.6 and 11.2 months, respectively. Conclusions M-PHP using the GEN 2 filter can achieve a high ORR and prolonged survival in patients with liver-only ocular melanoma metastases.

Percutaneous hepatic melphalan perfusion: Single center experience of procedural characteristics, hemodynamic response, complications, and postoperative recovery

“…Our results suggested that the perioperative management of PHMP is frequently associated with procedure-related issues. These findings are in similarity with previous studies from other centers [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. The main issues related to PHMP were hemodynamic depression, vascular access complications, and coagulopathy.…”

“…Fifty-three PHMP procedures of 16 patients were analyzed. In all of the cases, procedurerelated hypotension required the median (range) highest noradrenaline infusion rate of 0.5 (0.17-2.1) μg kg min -1 and fluid resuscitation volume of 5 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) liters. Eighty-four PHMPrelated complications were observed in 33 cases (62%), of which 9 cases (27%) involved grade III and IV complications.…”

“…Percutaneous hepatic melphalan perfusion (PHMP) is a third-line treatment option in patients with unresectable, isolated liver metastases or primary liver tumors [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Liver metastases and liver cancer tissues are primarily supplied by branches of the hepatic artery, whereas normal hepatocytes are supplied by the portal vein.…”

“…Although recent studies have shown promising long-term results, PHMP itself is reported to be associated with severe cardiovascular issues and potentially life-threatening adverse events, including myocardial infarction, cerebral stroke, and bleeding complications [1,[3][4][5][6][7][8][9][10][11][12][13][14][15]. Considerable hemodynamic instability can frequently occur after engagement of the filters and the clamping of the bypass circuit [3,13].…”

ASO Author Reflections: Percutaneous Hepatic Perfusion with Melphalan in Patients with Unresectable Hepatic Metastases from Ocular Melanoma

“…This prospective, phase II study investigated the efficacy and safety of M-PHP using the GEN 2 filter in well-selected patients with unresectable metastases from ocular melanoma confined to the liver. 5 Sixty-four M-PHP procedures were performed in 35 patients. The overall response rate of 72% (complete response 3%, partial response 69%) and median overall survival (OS) of 19.1 months in the current study appeared to be more favourable compared with published data on other treatment modalities and provide convincing evidence for the efficacy of M-PHP in metastatic ocular melanoma.…”