Marybeth S Hughes1, Jonathan Zager2, Mark Faries3, H Richard Alexander4, Richard E Royal5, Bradford Wood6, Junsung Choi2, Kevin McCluskey7, Eric Whitman8, Sanjiv Agarwala9, Gary Siskin10, Charles Nutting11, Mary Ann Toomey1, Carole Webb1, Tatiana Beresnev1, James F Pingpank12,13. 1. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. 2. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 3. John Wayne Cancer Institute, Providence St. John's Health Center, Santa Monica, CA, USA. 4. Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA. 5. M.D. Anderson Cancer Center, University of Texas, Houston, TX, USA. 6. Center for Interventional Oncology, National Institutes of Health, Bethesda, MD, USA. 7. University of Pittsburgh Schools of the Health Sciences, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. 8. Carol G. Simon Cancer Center, Atlantic Health System, Morristown, NJ, USA. 9. St. Luke's Cancer Center, Bethlehem, PA, USA. 10. Albany Medical Neurosciences Institute, Albany, NY, USA. 11. RIA Endovascular, Greenwood Village, CO, USA. 12. University of Pittsburgh Schools of the Health Sciences, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. pingpankjf@upmc.edu. 13. Division of Hepatobiliary Surgery, Surgical Oncology Services, Hillman Cancer Center, UPMC, Pittsburgh, PA, USA. pingpankjf@upmc.edu.
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.
RCT Entities:
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.
Authors: Akira Yamamoto; Inna Chervoneva; Kevin L Sullivan; David J Eschelman; Carin F Gonsalves; Michael J Mastrangelo; David Berd; Jerry A Shields; Carol L Shields; Mizue Terai; Takami Sato Journal: Radiology Date: 2009-07 Impact factor: 11.105
Authors: Georgia M Beasley; Paul Speicher; Christina K Augustine; Paul C Dolber; Bercedis L Peterson; Ketan Sharma; Paul J Mosca; Richard Royal; Merrick Ross; Jonathan S Zager; Douglas S Tyler Journal: Ann Surg Oncol Date: 2014-08-22 Impact factor: 5.344
Authors: D Gomez; C Wetherill; J Cheong; L Jones; E Marshall; B Damato; S E Coupland; P Ghaneh; G J Poston; H Z Malik; S W Fenwick Journal: J Surg Oncol Date: 2013-12-19 Impact factor: 3.454
Authors: James F Pingpank; Steven K Libutti; Richard Chang; Bradford J Wood; Ziv Neeman; Anthony W Kam; William D Figg; Souping Zhai; Tatiana Beresneva; Geoffrey D Seidel; H Richard Alexander Journal: J Clin Oncol Date: 2005-05-20 Impact factor: 44.544
Authors: R Olofsson; C Cahlin; C All-Ericsson; F Hashimi; J Mattsson; M Rizell; P Lindnér Journal: Ann Surg Oncol Date: 2013-10-19 Impact factor: 5.344
Authors: H Richard Alexander; Steven K Libutti; James F Pingpank; Seth M Steinberg; David L Bartlett; Cynthia Helsabeck; Tatiana Beresneva Journal: Clin Cancer Res Date: 2003-12-15 Impact factor: 12.531
Authors: Martha M Kirstein; Steffen Marquardt; Nils Jedicke; Silke Marhenke; Wolfgang Koppert; Michael P Manns; Frank Wacker; Arndt Vogel Journal: J Cancer Res Clin Oncol Date: 2017-06-20 Impact factor: 4.553
Authors: Brian A Boone; Samantha Perkins; Rupal Bandi; Ernesto Santos; Kevin McCluskey; David L Bartlett; James F Pingpank Journal: J Surg Oncol Date: 2018-04 Impact factor: 3.454
Authors: Andrea M Abbott; Matthew P Doepker; Youngchul Kim; Matthew C Perez; Cassandra Gandle; Kerry L Thomas; Junsung Choi; Ravi Shridhar; Jonathan S Zager Journal: Am J Clin Oncol Date: 2018-08 Impact factor: 2.339
Authors: Colin Yee; David McCoy; Jay Yu; Aaron Losey; Caroline Jordan; Terilyn Moore; Carol Stillson; Hee Jeung Oh; Bridget Kilbride; Shuvo Roy; Anand Patel; Mark W Wilson; Steven W Hetts Journal: Radiol Imaging Cancer Date: 2019-09-27
Authors: Steffen Marquardt; Martha M Kirstein; Roland Brüning; Martin Zeile; Pier Francesco Ferrucci; Warner Prevoo; Boris Radeleff; Hervé Trillaud; Lambros Tselikas; Emilio Vicente; Philipp Wiggermann; Michael P Manns; Arndt Vogel; Frank K Wacker Journal: Eur Radiol Date: 2018-09-25 Impact factor: 5.315
Authors: T Susanna Meijer; Lioe-Fee de Geus-Oei; Christian H Martini; Fred G J Tijl; M Elske Sitsen; Arian R van Erkel; Rutger W van der Meer; Ellen Kapiteijn; Alexander L Vahrmeijer; Mark C Burgmans Journal: Diagn Interv Radiol Date: 2019-11 Impact factor: 2.630