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

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

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1309-1319
Number of pages11
JournalAnnals of Surgical Oncology
Volume23
Issue number4
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

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Melanoma
Patient Care
Melphalan
Perfusion
Neoplasm Metastasis
Liver
Disease-Free Survival
Survival
Hepatic Artery

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Hughes, Marybeth S. ; Zager, Jonathan ; Faries, Mark ; Alexander, H. Richard ; Royal, Richard E. ; Wood, Bradford ; Choi, Junsung ; McCluskey, Kevin ; Whitman, Eric ; Agarwala, Sanjiv ; Siskin, Gary ; Nutting, Charles ; Toomey, Mary Ann ; Webb, Carole ; Beresnev, Tatiana ; Pingpank, James F. / Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases. In: Annals of Surgical Oncology. 2016 ; Vol. 23, No. 4. pp. 1309-1319.
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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",
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.",
author = "Hughes, {Marybeth S.} and Jonathan Zager and Mark Faries and Alexander, {H. Richard} and Royal, {Richard E.} and Bradford Wood and Junsung Choi and Kevin McCluskey and Eric Whitman and Sanjiv Agarwala and Gary Siskin and Charles Nutting and Toomey, {Mary Ann} and Carole Webb and Tatiana Beresnev and Pingpank, {James F.}",
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Hughes, MS, Zager, J, Faries, M, Alexander, HR, Royal, RE, Wood, B, Choi, J, McCluskey, K, Whitman, E, Agarwala, S, Siskin, G, Nutting, C, Toomey, MA, Webb, C, Beresnev, T & Pingpank, JF 2016, 'Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases', Annals of Surgical Oncology, vol. 23, no. 4, pp. 1309-1319. https://doi.org/10.1245/s10434-015-4968-3

Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases. / Hughes, Marybeth S.; Zager, Jonathan; Faries, Mark; Alexander, H. Richard; Royal, Richard E.; Wood, Bradford; Choi, Junsung; McCluskey, Kevin; Whitman, Eric; Agarwala, Sanjiv; Siskin, Gary; Nutting, Charles; Toomey, Mary Ann; Webb, Carole; Beresnev, Tatiana; Pingpank, James F.

In: Annals of Surgical Oncology, Vol. 23, No. 4, 01.04.2016, p. 1309-1319.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Results of a Randomized Controlled Multicenter Phase III Trial of Percutaneous Hepatic Perfusion Compared with Best Available Care for Patients with Melanoma Liver Metastases

AU - Hughes, Marybeth S.

AU - Zager, Jonathan

AU - Faries, Mark

AU - Alexander, H. Richard

AU - Royal, Richard E.

AU - Wood, Bradford

AU - Choi, Junsung

AU - McCluskey, Kevin

AU - Whitman, Eric

AU - Agarwala, Sanjiv

AU - Siskin, Gary

AU - Nutting, Charles

AU - Toomey, Mary Ann

AU - Webb, Carole

AU - Beresnev, Tatiana

AU - Pingpank, James F.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

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