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

Ioannis Karydis, Alexandra Gangi, Matthew J Wheater, Junsung Choi, Iain Wilson, Kerry Thomas, Neil Pearce, Arjun Takhar, Sanjay Gupta, Danielle Hardman, Sean Sileno, Brian Stedman, Jonathan S Zager, Christian Ottensmeier, Ioannis Karydis, Alexandra Gangi, Matthew J Wheater, Junsung Choi, Iain Wilson, Kerry Thomas, Neil Pearce, Arjun Takhar, Sanjay Gupta, Danielle Hardman, Sean Sileno, Brian Stedman, Jonathan S Zager, Christian Ottensmeier

Abstract

Background: Metastatic 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.

Methods: Retrospective 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.

Results: A 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).

Conclusions: M-PHP results in durable intrahepatic disease control and can form the basis for an integrated multimodality treatment approach in appropriately selected UM patients.

Keywords: chemosaturation; intrahepatic percutaneous haemoperfusion; liver metastasis; melphalan; unresectable liver tumor; uveal melanoma.

© 2017 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
M‐PHP circuit
Figure 2
Figure 2
Waterfall plot of the best objective hepatic response to M‐PHP, measured as the maximum change from baseline in the sum of the longest diameter of each liver target lesion
Figure 3
Figure 3
Kaplan‐Meier plots of overall survival of UM patients treated with M‐PHP. (A) Curve for entire group. (B‐D) Curves stratified by best response to M‐PHP (B), disease burden at baseline (C) and serum LDH (D)
Figure 4
Figure 4
Kaplan–Meier plots of overall and hepatic progression free survival of UM patients treated with M‐PHP. (A) Curves for entire group, median PFS and hPFS not reached. (B‐F) Curves stratified by best response to M‐PHP (B), serum LDH (B), disease burden at baseline (D) and previous systemic (E) or liver‐directed (F) treatment

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