Annals of Surgical Oncology

, Volume 23, Issue 4, pp 1309–1319 | Cite as

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
Hepatobiliary Tumors

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.

Keywords

Melanoma Overall Survival Cutaneous Melanoma Bone Marrow Suppression Regional Therapy 

Notes

Acknowledgment

The authors would like to acknowledge all of the patients and their families for participation in this clinical trial. In addition, we would like to thank all of the interventional radiologists, nurses, and physicians who helped provide excellent care to our patients. This study was funded by the Intramural Program of the National Cancer Institute, National Institutes of Health. Additional funding was supplied via a Cooperative Research and Development Agreement (CRADA) between Delcath Systems, Inc., and the Surgery Branch of the National Cancer Institute.

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Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Marybeth S. Hughes
    • 1
  • Jonathan Zager
    • 2
  • Mark Faries
    • 3
  • H. Richard Alexander
    • 4
  • Richard E. Royal
    • 5
  • Bradford Wood
    • 6
  • Junsung Choi
    • 2
  • Kevin McCluskey
    • 7
  • Eric Whitman
    • 8
  • Sanjiv Agarwala
    • 9
  • Gary Siskin
    • 10
  • Charles Nutting
    • 11
  • Mary Ann Toomey
    • 1
  • Carole Webb
    • 1
  • Tatiana Beresnev
    • 1
  • James F. Pingpank
    • 7
    • 12
  1. 1.Center for Cancer ResearchNational Cancer InstituteBethesdaUSA
  2. 2.H. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  3. 3.John Wayne Cancer InstituteProvidence St. John’s Health CenterSanta MonicaUSA
  4. 4.Marlene and Stewart Greenebaum Cancer CenterUniversity of MarylandBaltimoreUSA
  5. 5.M.D. Anderson Cancer Center, University of TexasHoustonUSA
  6. 6.Center for Interventional OncologyNational Institutes of HealthBethesdaUSA
  7. 7.University of Pittsburgh Schools of the Health SciencesUniversity of Pittsburgh Medical CenterPittsburghUSA
  8. 8.Carol G. Simon Cancer CenterAtlantic Health SystemMorristownUSA
  9. 9.St. Luke’s Cancer CenterBethlehemUSA
  10. 10.Albany Medical Neurosciences InstituteAlbanyUSA
  11. 11.RIA EndovascularGreenwood VillageUSA
  12. 12.Division of Hepatobiliary Surgery, Surgical Oncology Services, Hillman Cancer CenterUPMCPittsburghUSA

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