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

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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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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Authors and Affiliations

  1. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    Marybeth S. Hughes MD, Mary Ann Toomey RN, Carole Webb RN & Tatiana Beresnev MD

  2. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Jonathan Zager MD & Junsung Choi MD

  3. John Wayne Cancer Institute, Providence St. John’s Health Center, Santa Monica, CA, USA

    Mark Faries MD

  4. Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA

    H. Richard Alexander MD

  5. M.D. Anderson Cancer Center, University of Texas, Houston, TX, USA

    Richard E. Royal MD

  6. Center for Interventional Oncology, National Institutes of Health, Bethesda, MD, USA

    Bradford Wood MD

  7. University of Pittsburgh Schools of the Health Sciences, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Kevin McCluskey MD & James F. Pingpank MD, FACS

  8. Carol G. Simon Cancer Center, Atlantic Health System, Morristown, NJ, USA

    Eric Whitman MD

  9. St. Luke’s Cancer Center, Bethlehem, PA, USA

    Sanjiv Agarwala MD

  10. Albany Medical Neurosciences Institute, Albany, NY, USA

    Gary Siskin MD

  11. RIA Endovascular, Greenwood Village, CO, USA

    Charles Nutting DO

  12. Division of Hepatobiliary Surgery, Surgical Oncology Services, Hillman Cancer Center, UPMC, Pittsburgh, PA, USA

    James F. Pingpank MD, FACS

Authors
  1. Marybeth S. Hughes MD
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  2. Jonathan Zager MD
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  3. Mark Faries MD
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  4. H. Richard Alexander MD
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  5. Richard E. Royal MD
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  6. Bradford Wood MD
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  7. Junsung Choi MD
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  8. Kevin McCluskey MD
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  9. Eric Whitman MD
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  10. Sanjiv Agarwala MD
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  11. Gary Siskin MD
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  12. Charles Nutting DO
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  13. Mary Ann Toomey RN
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  14. Carole Webb RN
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  15. Tatiana Beresnev MD
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  16. James F. Pingpank MD, FACS
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Corresponding author

Correspondence to James F. Pingpank MD, FACS.

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Hughes, M.S., Zager, J., Faries, M. et al. 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 23, 1309–1319 (2016). https://doi.org/10.1245/s10434-015-4968-3

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  • DOI: https://doi.org/10.1245/s10434-015-4968-3

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