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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2016

01-04-2016 | Hepatobiliary Tumors

Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases

Authors: Marybeth S. Hughes, MD, Jonathan Zager, MD, Mark Faries, MD, H. Richard Alexander, MD, Richard E. Royal, MD, Bradford Wood, MD, Junsung Choi, MD, Kevin McCluskey, MD, Eric Whitman, MD, Sanjiv Agarwala, MD, Gary Siskin, MD, Charles Nutting, DO, Mary Ann Toomey, RN, Carole Webb, RN, Tatiana Beresnev, MD, James F. Pingpank, MD, FACS

Published in: Annals of Surgical Oncology | Issue 4/2016

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Abstract

Purpose

There is no consensus for the treatment of melanoma metastatic to the liver. Percutaneous hepatic perfusion with melphalan (PHP-Mel) is a method of delivering regional chemotherapy selectively to the liver. In this study, we report the results of a multicenter, randomized controlled trial comparing PHP-Mel with best alternative care (BAC) for patients with ocular or cutaneous melanoma metastatic to the liver.

Patients and Methods

A total of 93 patients were randomized to PHP-Mel (n = 44) or BAC (n = 49). On the PHP-Mel arm, melphalan was delivered via the hepatic artery, and the hepatic effluent captured and filtered extracorporeally prior to return to the systemic circulation via a venovenous bypass circuit. PHP-Mel was repeatable every 4–8 weeks. The primary endpoint was hepatic progression-free survival (hPFS), and secondary endpoints included overall PFS (oPFS), overall survival (OS), hepatic objective response (hOR), and safety.

Results

hPFS was 7.0 months for PHP-Mel and 1.6 months for BAC (p < 0.0001), while oPFS was 5.4 months for PHP-Mel and 1.6 months for BAC (p < 0.0001). Median OS was not significantly different (PHP-Mel 10.6 months vs. BAC 10.0 months), likely due to crossover to PHP-Mel treatment (57.1 %) from the BAC arm, and the hOR was 36.4 % for PHP-Mel and 2.0 % for BAC (p < 0.001). The majority of adverse events were related to bone marrow suppression. Four deaths were attributed to PHP-Mel, three in the primary PHP-Mel group, and one post-crossover to PHP-Mel from BAC.

Conclusion

This randomized, phase III study demonstrated the efficacy of the PHP-Mel procedure. hPFS, oPFS, and hOR were significantly improved with PHP-Mel. PHP with melphalan should provide a new treatment option for unresectable metastatic melanoma in the liver.
Literature
1.
Karlen AI, Clark JJ, Wong LL. Two cases of partial hepatectomy for malignant melanoma. Hawaii J Med Public Health. 2012;71:92–6PubMedPubMedCentral
2.
Damato B. Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture. Eye (Lond). 2012;26:1157–72CrossRef
3.
Feldman ED, Pingpank JF, Alexander HR Jr. Regional treatment options for patients with ocular melanoma metastatic to the liver. Ann Surg Oncol. 2004;11:290–7CrossRefPubMed
4.
Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S, Stefanovic V. Ocular melanoma: an overview of the current status. Int J Clin Exp Pathol. 2013;6:1230–44PubMedPubMedCentral
5.
Alexander HR Jr, Libutti SK, Pingpank JF, Steinberg SM, Bartlett DL, Helsabeck C. Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2003;9:6343–9PubMed
6.
Pereira PR, Odashiro AN, Lim LA, Miyamoto C, Blanco PL, Odashiro M, et al. Current and emerging treatment options for uveal melanoma. Clin Ophthalmol. 2013;7:1669–82CrossRefPubMedPubMedCentral
7.
Forster MR, Rashid OM, Perez MC, Choi J, Chaudhry T, Zager J, et al. Chemosaturation with percutaneous hepatic perfusion for unresectable metastatic melanoma or sarcoma to the liver: a single institution experience. J Surg Oncol. 2014;109:434–9CrossRefPubMedPubMedCentral
8.
Rashid OM, Sloot S, Zager JS. Regional therapy in metastatic melanoma: an update on minimally invasive intraarterial isolated limb infusion and percutaneous hepatic perfusion. Expert Opin Drug Metab Toxicol. 2014;10:1355–64CrossRefPubMed
9.
Gomez D, Wetherill C, Cheong J, Jones L, Marshall E, Damato B, et al. The liverpool uveal melanoma liver metastases pathway: outcome following liver resection. J Surg Oncol. 2014;109:542–7CrossRefPubMed
10.
Frenkel S, Nir I, Hendler K, Lotem M, Eid A, Jurim O, et al. Long-term survival of uveal melanoma patients after surgery for liver metastases. Br J Ophthalmol. 2009;93:1042–6CrossRefPubMed
11.
Klingenstein A, Haug AR, Zech CJ, Schaller UC. Radioembolization as locoregional therapy of hepatic metastases in uveal melanoma patients. Cardiovasc Interv Radiol. 2013;36:158–65CrossRef
12.
Gonsalves CF, Eschelman DJ, Sullivan KL, Anne PR, Doyle L, Sato T. Radioembolization as salvage therapy for hepatic metastasis of uveal melanoma: a single-institution experience. AJR Am J Roentgenol. 2011;196:468–73CrossRefPubMed
13.
Yamamoto A, Chervoneva I, Sullivan KL, Eschelman DJ, Gonsalves CF, Mastrangelo MJ, et al. High-dose immunoembolization: survival benefit in patients with hepatic metastases from uveal melanoma. Radiology. 2009;252:290–8CrossRefPubMed
14.
Sato T, Eschelman DJ, Gonsalves CF, Terai M, Chervoneva I, McCue PA, et al. Immunoembolization of malignant liver tumors, including uveal melanoma, using granulocyte-macrophage colony-stimulating factor. J Clin Oncol. 2008;26:5436–42CrossRefPubMed
15.
Agarwala SS, Eggermont AM, O’Day S, Zager JS. Metastatic melanoma to the liver: a contemporary and comprehensive review of surgical, systemic, and regional therapeutic options. Cancer. 2014;120:781–9CrossRefPubMed
16.
Han D, Beasley GM, Tyler DS, Zager JS. Minimally invasive intra-arterial regional therapy for metastatic melanoma: isolated limb infusion and percutaneous hepatic perfusion. Expert Opin Drug Metab Toxicol. 2011;7:1383–94CrossRefPubMedPubMedCentral
17.
Alexander HR, Libutti SK, Bartlett DL, Puhlmann M, Fraker DL, Bachenheimer LC. A phase I–II study of isolated hepatic perfusion using melphalan with or without tumor necrosis factor for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2000;6:3062–70PubMed
18.
Olofsson R, Cahlin C, All-Ericsson C, Hashimi F, Mattsson J, Rizell M, et al. Isolated hepatic perfusion for ocular melanoma metastasis: registry data suggests a survival benefit. Ann Surg Oncol. 2014;21:466–72CrossRefPubMed
19.
Pingpank JF, Libutti SK, Chang R, Wood BJ, Neeman Z, Kam AW, et al. 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;23:3465–74CrossRefPubMedPubMedCentral
20.
Yamamoto M, Zager JS. Isolated hepatic perfusion for metastatic melanoma. J Surg Oncol. 2014;109:383–8CrossRefPubMed
21.
Paulsen IF, Chakera AH, Drejoe JB, Klyver H, Dahlstrøm K, Oturai P, et al. Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma. Dan Med J. 2014;61:A4741PubMed
22.
Steinman J, Ariyan C, Rafferty B, Brady MS. Factors associated with response, survival, and limb salvage in patients undergoing isolated limb infusion. J Surg Oncol. 2014;109:405–9CrossRefPubMed
23.
Wong J, Chen YA, Fisher KJ, Beasley GM, Tyler DS, Zager JS. Resection of residual disease after isolated limb infusion (ILI) is equivalent to a complete response after ILI-alone in advanced extremity melanoma. Ann Surg Oncol. 2014;21:650–5CrossRefPubMedPubMedCentral
24.
Beasley GM, Speicher P, Augustine CK, Dolber PC, Peterson BL, Sharma K, et al. A multicenter phase I dose escalation trial to evaluate safety and tolerability of intra-arterial temozolomide for patients with advanced extremity melanoma using normothermic isolated limb infusion. Ann Surg Oncol. 2015;22:287–94CrossRefPubMedPubMedCentral
25.
Leyvraz S, Spataro V, Bauer J, Pampallona S, Salmon R, Dorval T, et al. Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy. J Clin Oncol. 1997;15:2589–95PubMed
26.
27.
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23CrossRefPubMedPubMedCentral
28.
Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369:134–44CrossRefPubMedPubMedCentral
29.
Danielli R, Ridolfi R, Chiarion-Sileni V, Queirolo P, Testori A, Plummer R. Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy. Cancer Immunol Immunother. 2012;61:41–8CrossRefPubMed
Metadata
Title
Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases
Authors
Marybeth S. Hughes, MD
Jonathan Zager, MD
Mark Faries, MD
H. Richard Alexander, MD
Richard E. Royal, MD
Bradford Wood, MD
Junsung Choi, MD
Kevin McCluskey, MD
Eric Whitman, MD
Sanjiv Agarwala, MD
Gary Siskin, MD
Charles Nutting, DO
Mary Ann Toomey, RN
Carole Webb, RN
Tatiana Beresnev, MD
James F. Pingpank, MD, FACS
Publication date
01-04-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 4/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4968-3

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