Percutaneous Hepatic Perfusion with Melphalan in Uveal Melanoma: A Safe and Effective Treatment Modality in an Orphan Disease

Overview

Journal J Surg Oncol

Specialties General Surgery
Oncology

Date 2017 Dec 29

PMID 29284076

Citations 41

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Imipridones inhibit tumor growth and improve survival in an orthotopic liver metastasis mouse model of human uveal melanoma.

Chattopadhyay C, Roszik J, Bhattacharya R, Alauddin M, Mahmud I, Yadugiri S Br J Cancer. 2024; 131(11):1846-1857.

PMID: 39394450 PMC: 11589887. DOI: 10.1038/s41416-024-02866-6.

Hepatic and Overall Progression-Free Survival After Percutaneous Hepatic Perfusion (PHP) as First-Line or Second-Line Therapy for Metastatic Uveal Melanoma.

Ghali H, Dugan M, Aflatooni S, Boby A, DePalo D, Laborde J Ann Surg Oncol. 2024; 31(13):9150-9158.

PMID: 39174837 DOI: 10.1245/s10434-024-16039-5.

Clinical Characteristics and Special Considerations in the Management of Rare Melanoma Subtypes.

Shannon A, Zager J, Perez M Cancers (Basel). 2024; 16(13).

PMID: 39001457 PMC: 11240680. DOI: 10.3390/cancers16132395.

The Current State of Systemic Therapy of Metastatic Uveal Melanoma.

Koch E, Heppt M, Berking C Am J Clin Dermatol. 2024; 25(5):691-700.

PMID: 38907174 PMC: 11358228. DOI: 10.1007/s40257-024-00872-1.

Intralesional and Infusional Updates for Metastatic Melanoma.

Dugan M, Shannon A, DePalo D, Perez M, Zager J Cancers (Basel). 2024; 16(11).

PMID: 38893078 PMC: 11171204. DOI: 10.3390/cancers16111957.

References

Long G, Weber J, Infante J, Kim K, Daud A, Gonzalez R . Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib. J Clin Oncol. 2016; 34(8):871-8. DOI: 10.1200/JCO.2015.62.9345. View

Lodh S, Maher R, Guminski A . Intra-arterial infusion and chemo-embolization for melanoma liver metastases. J Surg Oncol. 2014; 109(4):376-82. DOI: 10.1002/jso.23551. View

Sigurdson E, Ridge J, Kemeny N, Daly J . Tumor and liver drug uptake following hepatic artery and portal vein infusion. J Clin Oncol. 1987; 5(11):1836-40. DOI: 10.1200/JCO.1987.5.11.1836. View

Chan T, Wiltrout R, Weiss J . Immunotherapeutic modulation of the suppressive liver and tumor microenvironments. Int Immunopharmacol. 2011; 11(7):879-89. PMC: 3082592. DOI: 10.1016/j.intimp.2010.12.024. View

Abbott A, Doepker M, Kim Y, Perez M, Gandle C, Thomas K . Hepatic Progression-free and Overall Survival After Regional Therapy to the Liver for Metastatic Melanoma. Am J Clin Oncol. 2017; 41(8):747-753. PMC: 7771287. DOI: 10.1097/COC.0000000000000356. View

Agarwala S, Eggermont A, ODay S, Zager J . Metastatic melanoma to the liver: a contemporary and comprehensive review of surgical, systemic, and regional therapeutic options. Cancer. 2013; 120(6):781-9. DOI: 10.1002/cncr.28480. View

Pingpank J, Libutti S, Chang R, Wood B, Neeman Z, Kam A . Phase I study of hepatic arterial melphalan infusion and hepatic venous hemofiltration using percutaneously placed catheters in patients with unresectable hepatic malignancies. J Clin Oncol. 2005; 23(15):3465-74. PMC: 2374756. DOI: 10.1200/JCO.2005.00.927. View

Helgadottir H, Hoiom V . The genetics of uveal melanoma: current insights. Appl Clin Genet. 2016; 9:147-55. PMC: 5019476. DOI: 10.2147/TACG.S69210. View

Kelderman S, van der Kooij M, van den Eertwegh A, Soetekouw P, Jansen R, van den Brom R . Ipilimumab in pretreated metastastic uveal melanoma patients. Results of the Dutch Working group on Immunotherapy of Oncology (WIN-O). Acta Oncol. 2013; 52(8):1786-8. DOI: 10.3109/0284186X.2013.786839. View

10.

Kath R, Hayungs J, Bornfeld N, Sauerwein W, Hoffken K, Seeber S . Prognosis and treatment of disseminated uveal melanoma. Cancer. 1993; 72(7):2219-23. DOI: 10.1002/1097-0142(19931001)72:7<2219::aid-cncr2820720725>3.0.co;2-j. View

11.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

12.

Gomez D, Wetherill C, Cheong J, Jones L, Marshall E, Damato B . The Liverpool uveal melanoma liver metastases pathway: outcome following liver resection. J Surg Oncol. 2013; 109(6):542-7. DOI: 10.1002/jso.23535. View

13.

Algazi A, Tsai K, Shoushtari A, Munhoz R, Eroglu Z, Piulats J . Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies. Cancer. 2016; 122(21):3344-3353. PMC: 5767160. DOI: 10.1002/cncr.30258. View

14.

Nathan P, Cohen V, Coupland S, Curtis K, Damato B, Evans J . Uveal Melanoma UK National Guidelines. Eur J Cancer. 2015; 51(16):2404-12. DOI: 10.1016/j.ejca.2015.07.013. View

15.

Alexander Jr H, Libutti S, Pingpank J, Steinberg S, Bartlett D, Helsabeck C . Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2003; 9(17):6343-9. View

16.

Diener-West M, Reynolds S, Agugliaro D, Caldwell R, Cumming K, Earle J . Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005; 123(12):1639-43. DOI: 10.1001/archopht.123.12.1639. View

17.

Karydis I, Chan P, Wheater M, Arriola E, Szlosarek P, Ottensmeier C . Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma. Oncoimmunology. 2016; 5(5):e1143997. PMC: 4910726. DOI: 10.1080/2162402X.2016.1143997. View

18.

Yamamoto M, Zager J . Isolated hepatic perfusion for metastatic melanoma. J Surg Oncol. 2013; 109(4):383-8. DOI: 10.1002/jso.23474. View

19.

Hughes M, Zager J, Faries M, Alexander H, Royal R, Wood B . Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases. Ann Surg Oncol. 2015; 23(4):1309-19. PMC: 8185532. DOI: 10.1245/s10434-015-4968-3. View

20.

Zimmer L, Vaubel J, Mohr P, Hauschild A, Utikal J, Simon J . Phase II DeCOG-study of ipilimumab in pretreated and treatment-naïve patients with metastatic uveal melanoma. PLoS One. 2015; 10(3):e0118564. PMC: 4356548. DOI: 10.1371/journal.pone.0118564. View