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: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Marybeth S
authors.initials: MS
authors.lastname: Hughes
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Zager
authors.affiliation: John Wayne Cancer Institute, Providence St. John's Health Center, Santa Monica, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Faries
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA.
authors.forename: H Richard
authors.initials: HR
authors.lastname: Alexander
authors.affiliation: M.D. Anderson Cancer Center, University of Texas, Houston, TX, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Royal
authors.affiliation: Center for Interventional Oncology, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Bradford
authors.initials: B
authors.lastname: Wood
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Junsung
authors.initials: J
authors.lastname: Choi
authors.affiliation: University of Pittsburgh Schools of the Health Sciences, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: McCluskey
authors.affiliation: Carol G. Simon Cancer Center, Atlantic Health System, Morristown, NJ, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Whitman
authors.affiliation: St. Luke's Cancer Center, Bethlehem, PA, USA.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Agarwala
authors.affiliation: Albany Medical Neurosciences Institute, Albany, NY, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Siskin
authors.affiliation: RIA Endovascular, Greenwood Village, CO, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Nutting
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Toomey
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Webb
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Beresnev
authors.affiliation: University of Pittsburgh Schools of the Health Sciences, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. pingpankjf@upmc.edu.|Division of Hepatobiliary Surgery, Surgical Oncology Services, Hillman Cancer Center, UPMC, Pittsburgh, PA, USA. pingpankjf@upmc.edu.
authors.forename: James F
authors.initials: JF
authors.lastname: Pingpank
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D010478:Chemotherapy, Cancer, Regional Perfusion; D004621:Embolization, Therapeutic; D005134:Eye Neoplasms / Q000188:drug therapy / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D010477:Perfusion; D011379:Prognosis; D012878:Skin Neoplasms / Q000188:drug therapy / Q000556:secondary*; D015996:Survival Rate