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Contemporary Liver Transplantation pp 303–316Cite as

Systemic Chemotherapy in Orthotopic Liver Transplantation

  • Reference work entry
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Part of the book series: Organ and Tissue Transplantation ((OTT))

Abstract

The management of hepatocellular carcinoma (HCC) is complex, requiring a multidisciplinary approach with surgeons, hepatologists, medical oncologists, radiation oncologists, and interventional radiologists. Patients with HCC often have concurrent liver disease, further complicating their management. Options for therapy range from potentially curative resection and orthotopic liver transplantation (OLT), local ablative therapies, trans-arterial embolization, and systemic therapy. A number of treatment algorithms have been developed to aid in the management of HCC, including the Barcelona Clinic Liver Cancer (BCLC) staging system. This model incorporates liver function, performance status, and tumor characteristics. It also includes treatment recommendations based on BCLC stage. Included in the algorithm is OLT for eligible patients with early stage disease, and sorafenib as systemic therapy for advanced stage disease. It does not, however, include recommendations about the combination of these two treatments. This chapter will review literature for the use of systemic therapy combined with OLT for HCC, as well as for the use of systemic therapy in the event of relapse after OLT. Additionally, a review of systemic therapy in combination with OLT for cholangiocarcinoma and neuroendocrine tumors is included.

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References

  • Abou-Alfa GK, Venook AP (2013) The antiangiogenic ceiling in hepatocellular carcinoma: does it exist and has it been reached? Lancet Oncol 14(7):e283–e288

    Article  CAS  PubMed  Google Scholar 

  • Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB (2006) Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24(26):4293–4300

    Article  CAS  PubMed  Google Scholar 

  • Adair A, Wigmore SJ (2013) Sorafenib for hepatocellular carcinoma before liver transplantation. Transpl Int 26(11):e100–e101

    Article  CAS  PubMed  Google Scholar 

  • Bassanello M, Vitale A, Ciarleglio FA, Brolese A, Zanus G, D’amico F, Carraro A, Cappuzzo G, Bridda A, Senzolo M, Burra P, Pevere S, D’amico D, Cillo U (2003) Adjuvant chemotherapy for transplanted hepatocellular carcinoma patients: impact on survival or HCV recurrence timing. Transplant Proc 35(8):2991–2994

    Article  CAS  PubMed  Google Scholar 

  • Bernal E, Montero JL, Delgado M, Fraga E, Costan G, Barrera P, Lopez-Vallejos P, Solorzano G, Rufian S, Briceno J, Padillo J, Lopez-Cillero P, Marchal T, Muntane J, De La Mata M (2006) Adjuvant chemotherapy for prevention of recurrence of invasive hepatocellular carcinoma after orthotopic liver transplantation. Transplant Proc 38(8):2495–2498

    Article  CAS  PubMed  Google Scholar 

  • Bismuth H, Chiche L, Adam R, Castaing D, Diamond T, Dennison A (1993) Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients. Ann Surg 218(2):145–151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Busuttil RW (2015), Sorafenib tosylate following a liver transplant in treating patients with liver cancer. (Homepage of ClinicalTrials.gov), [Online]. Available https://clinicaltrials.gov/ct2/show/NCT01624285?term=sorafenib+adjuvant&rank=2. Accessed 2015.

  • Cainap C, Qin S, Huang WT, Chung IJ, Pan H, Cheng Y, Kudo M, Kang YK, Chen PJ, Toh HC, Gorbunova V, Eskens FA, Qian J, Mckee MD, Ricker JL, Carlson DM, El-Nowiem S (2015) Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol 33(2):172–179

    Article  CAS  PubMed  Google Scholar 

  • Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10(1):25–34

    Article  CAS  PubMed  Google Scholar 

  • Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, Chung HC, Song X, Xu J, Poggi G, Omata M, Pitman Lowenthal S, Lanzalone S, Yang L, Lechuga MJ, Raymond E (2013) Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 31(32):4067–4075

    Article  CAS  PubMed  Google Scholar 

  • Cheng Al, Thongprasert S, Lim Hy et al (2015) Phase II study of front-line dovitinib (TKI258) versus sorafenib in patients (Pts) with advanced hepatocellular carcinoma (HCC). J Clin Oncol 33 (Suppl 3). Abstract 237

    Google Scholar 

  • Cherqui D, Piedbois P, Pierga JY, Duvoux C, Vavasseur D, Tran Van-Nhieu J, Lebourgeois JP, Julien M, Fagniez PL, Dhumeaux D (1994) Multimodal adjuvant treatment and liver transplantation for advanced hepatocellular carcinoma. A pilot study. Cancer 73(11):2721–2726

    Article  CAS  PubMed  Google Scholar 

  • Darwish Murad S, Kim WR, Harnois DM, Douglas DD, Burton J, Kulik LM, Botha JF, Mezrich JD, Chapman WC, Schwartz JJ, Hong JC, Emond JC, Jeon H, Rosen CB, Gores GJ, Heimbach JK (2012) Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers. Gastroenterology 143(1):88–98, e3; quiz e14

    Article  PubMed  Google Scholar 

  • De La Revilla NJ, Moreno JM, Rubio E, De Herreros TA, Navarrete E, Lopez MJ, Turrion VS, Jimenez M, Lucena M, Cuervas-Mons V (2003) Usefulness of chemotherapy as prophylaxis of tumor recurrence after liver transplantation in advanced hepatocellular carcinomas. Transplant Proc 35(5):1830–1831

    Article  PubMed  Google Scholar 

  • Di Marco V, De Vita F, Koskinas J, Semela D, Toniutto P, Verslype C (2013) Sorafenib: from literature to clinical practice. Ann Oncol 24(Suppl 2):ii30–ii37

    Article  PubMed  Google Scholar 

  • Edeline J, Boucher E, Rolland Y, Vauleon E, Pracht M, Perrin C, Le Roux C, Raoul JL (2012) Comparison of tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST in patients treated with sorafenib for hepatocellular carcinoma. Cancer 118(1):147–156

    Article  CAS  PubMed  Google Scholar 

  • European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56(4):908–943

    Article  Google Scholar 

  • Finn RS (2012) Sorafenib use while waiting for liver transplant: we still need to wait. J Hepatol 56(3):723–725

    Article  PubMed  Google Scholar 

  • Florman S, Toure B, Kim L, Gondolesi G, Roayaie S, Krieger N, Fishbein T, Emre S, Miller C, Schwartz M (2004) Liver transplantation for neuroendocrine tumors. J Gastrointest Surg 8(2):208–212

    Article  PubMed  Google Scholar 

  • Forner A, Reig ME, De Lope CR, Bruix J (2010) Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis 30(1):61–74

    Article  CAS  PubMed  Google Scholar 

  • Frenette CT, Boktour M, Burroughs SG, Kaseb A, Aloia TA, Galati J, Gaber AO, Monsour H Jr, Ghobrial RM (2013) Pre-transplant utilization of sorafenib is not associated with increased complications after liver transplantation. Transpl Int 26(7):734–739

    Article  CAS  PubMed  Google Scholar 

  • Fujiki M, Aucejo F, Choi M, Kim R (2014) Neo-adjuvant therapy for hepatocellular carcinoma before liver transplantation: where do we stand? World J Gastroenterol 20(18):5308–5319

    Article  PubMed  PubMed Central  Google Scholar 

  • Gedaly R, Daily MF, Davenport D, Mchugh PP, Koch A, Angulo P, Hundley JC (2011) Liver transplantation for the treatment of liver metastases from neuroendocrine tumors: an analysis of the UNOS database. Arch Surg 146(8):953–958

    Article  PubMed  Google Scholar 

  • Gomez-Martin C, Bustamante J, Castroagudin JF, Salcedo M, Garralda E, Testillano M, Herrero I, Matilla A, Sangro B (2012) Efficacy and safety of sorafenib in combination with mammalian target of rapamycin inhibitors for recurrent hepatocellular carcinoma after liver transplantation. Liver Transpl 18(1):45–52

    Article  PubMed  Google Scholar 

  • Gores GJ, Gish RG, Sudan D, Rosen CB, Meld Exception Study Group (2006) Model for end-stage liver disease (MELD) exception for cholangiocarcinoma or biliary dysplasia. Liver Transpl 12(12 Suppl 3):S95–S97

    Article  PubMed  Google Scholar 

  • Harding JJ, Abou-Alfa GK (2014) Treating advanced hepatocellular carcinoma: how to get out of first gear. Cancer 120(20):3122–3130

    Article  PubMed  Google Scholar 

  • Hoffmann K, Glimm H, Radeleff B, Richter G, Heining C, Schenkel I, Zahlten-Hinguranage A, Schirrmacher P, Schmidt J, Buchler MW, Jaeger D, Von Kalle C, Schemmer P (2008) Prospective, randomized, double-blind, multi-center, Phase III clinical study on transarterial chemoembolization (TACE) combined with Sorafenib versus TACE plus placebo in patients with hepatocellular cancer before liver transplantation – HeiLivCa [ISRCTN24081794]. BMC Cancer 8:349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hollebecque A, Malka D, Ferte C, Ducreux M, Boige V (2015) Systemic treatment of advanced hepatocellular carcinoma: from disillusions to new horizons. Eur J Cancer 51(3):327–339

    Article  PubMed  Google Scholar 

  • Holman M, Harrison D, Stewart A, Stone M, Goldstein R, Husberg B, Klintmalm G (1995) Neoadjuvant chemotherapy and orthotopic liver transplantation for hepatocellular carcinoma. N J Med 92(8):519–522

    CAS  PubMed  Google Scholar 

  • Hsieh CB, Chou SJ, Shih ML, Chu HC, Chu CH, Yu JC, Yao NS (2008) Preliminary experience with gemcitabine and cisplatin adjuvant chemotherapy after liver transplantation for hepatocellular carcinoma. Eur J Surg Oncol 34(8):906–910

    Article  PubMed  Google Scholar 

  • Huang X, Zheng Q, Yuan Z (2013) Neoadjuvant chemotherapy for hepatocellular carcinoma. In: Kaseb A (ed) Hepatocellular carcinoma – future outlook. InTech, Shanghai, China, pp 81–95

    Google Scholar 

  • Johnson PJ, Qin S, Park JW, Poon RT, Raoul JL, Philip PA, Hsu CH, Hu TH, Heo J, Xu J, Lu L, Chao Y, Boucher E, Han KH, Paik SW, Robles-Avina J, Kudo M, Yan L, Sobhonslidsuk A, Komov D, Decaens T, Tak WY, Jeng LB, Liu D, Ezzeddine R, Walters I, Cheng AL (2013) Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study. J Clin Oncol 31(28):3517–3524

    Article  CAS  PubMed  Google Scholar 

  • Kim R, El-Gazzaz G, Tan A, Elson P, Byrne M, Chang YD, Aucejo F (2010) Safety and feasibility of using sorafenib in recurrent hepatocellular carcinoma after orthotopic liver transplantation. Oncology 79(1–2):62–66

    Article  CAS  PubMed  Google Scholar 

  • Kornberg A, Kupper B, Tannapfel A, Katenkamp K, Thrum K, Habrecht O, Wilberg J (2010) Long-term survival after recurrent hepatocellular carcinoma in liver transplant patients: clinical patterns and outcome variables. Eur J Surg Oncol 36(3):275–280

    Article  CAS  PubMed  Google Scholar 

  • Lai CL, Wu PC, Lok AS, Lin HJ, Ngan H, Lau JY, Chung HT, Ng MM, Yeoh EK, Arnold M (1989) Recombinant alpha 2 interferon is superior to doxorubicin for inoperable hepatocellular carcinoma: a prospective randomised trial. Br J Cancer 60(6):928–933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lai CL, Lau JY, Wu PC, Ngan H, Chung HT, Mitchell SJ, Corbett TJ, Chow AW, Lin HJ (1993) Recombinant interferon-alpha in inoperable hepatocellular carcinoma: a randomized controlled trial. Hepatology 17(3):389–394

    Article  CAS  PubMed  Google Scholar 

  • Le Treut YP, Gregoire E, Klempnauer J, Belghiti J, Jouve E, Lerut J, Castaing D, Soubrane O, Boillot O, Mantion G, Homayounfar K, Bustamante M, Azoulay D, Wolf P, Krawczyk M, Pascher A, Suc B, Chiche L, De Urbina JO, Mejzlik V, Pascual M, Lodge JP, Gruttadauria S, Paye F, Pruvot FR, Thorban S, Foss A, Adam R, Elita F (2013) Liver transplantation for neuroendocrine tumors in Europe-results and trends in patient selection: a 213-case European liver transplant registry study. Ann Surg 257(5):807–815

    Article  PubMed  Google Scholar 

  • Lee JO, Kim DY, Lim JH, Seo MD, Yi HG, Oh DY, Im SA, Kim TY, Bang YJ (2009) Palliative chemotherapy for patients with recurrent hepatocellular carcinoma after liver transplantation. J Gastroenterol Hepatol 24(5):800–805

    Article  CAS  PubMed  Google Scholar 

  • Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30(1):52–60

    Article  CAS  PubMed  Google Scholar 

  • Lencioni R, Kudo M, Ye SL, Bronowicki JP, Chen XP, Dagher L, Furuse J, Geschwind JF, De Guevara LL, Papandreou C, Takayama T, Yoon SK, Nakajima K, Lehr R, Heldner S, Sanyal AJ (2014) GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and of its treatment with sorafeNib): second interim analysis. Int J Clin Pract 68(5):609–617

    Article  CAS  PubMed  Google Scholar 

  • Leung TW, Patt YZ, Lau WY, Ho SK, Yu SC, Chan AT, Mok TS, Yeo W, Liew CT, Leung NW, Tang AM, Johnson PJ (1999) Complete pathological remission is possible with systemic combination chemotherapy for inoperable hepatocellular carcinoma. Clin Cancer Res 5(7):1676–1681

    CAS  PubMed  Google Scholar 

  • Leung TW, Tang AM, Zee B, Yu SC, Lai PB, Lau WY, Johnson PJ (2002) Factors predicting response and survival in 149 patients with unresectable hepatocellular carcinoma treated by combination cisplatin, interferon-alpha, doxorubicin and 5-fluorouracil chemotherapy. Cancer 94(2):421–427

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Sala M, Castells L, Suarez Y, Vilana R, Bianchi L, Ayuso C, Vargas V, Rodes J, Bruix J (2000) Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma. Hepatology 31(1):54–58

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ, Panel of Experts in HCC-Design Clinical Trials (2008a) Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 100(10):698–711

    Article  PubMed  Google Scholar 

  • Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, De Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J, Sharp Investigators Study Group (2008b) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Decaens T, Raoul JL, Boucher E, Kudo M, Chang C, Kang YK, Assenat E, Lim HY, Boige V, Mathurin P, Fartoux L, Lin DY, Bruix J, Poon RT, Sherman M, Blanc JF, Finn RS, Tak WY, Chao Y, Ezzeddine R, Liu D, Walters I, Park JW (2013) Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. J Clin Oncol 31(28):3509–3516

    Article  CAS  PubMed  Google Scholar 

  • Maddala YK, Stadheim L, Andrews JC, Burgart LJ, Rosen CB, Kremers WK, Gores G (2004) Drop-out rates of patients with hepatocellular cancer listed for liver transplantation: outcome with chemoembolization. Liver Transpl 10(3):449–455

    Article  PubMed  Google Scholar 

  • Mazzaferro V, Pulvirenti A, Coppa J (2007) Neuroendocrine tumors metastatic to the liver: how to select patients for liver transplantation? J Hepatol 47(4):460–466

    Article  PubMed  Google Scholar 

  • Meyer CG, Penn I, James L (2000) Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation 69(8):1633–1637

    Article  CAS  PubMed  Google Scholar 

  • Nowak AK, Chow PK, Findlay M (2004) Systemic therapy for advanced hepatocellular carcinoma: a review. Eur J Cancer 40(10):1474–1484

    Article  CAS  PubMed  Google Scholar 

  • O’neil BH, Goff LW, Kauh JS, Strosberg JR, Bekaii-Saab TS, Lee RM, Kazi A, Moore DT, Learoyd M, Lush RM, Sebti SM, Sullivan DM (2011) Phase II study of the mitogen-activated protein kinase 1/2 inhibitor selumetinib in patients with advanced hepatocellular carcinoma. J Clin Oncol 29(17):2350–2356

    Article  PubMed  PubMed Central  Google Scholar 

  • Olthoff KM, Rosove MH, Shackleton CR, Imagawa DK, Farmer DG, Northcross P, Pakrasi AL, Martin P, Goldstein LI, Shaked A (1995) Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma. Ann Surg 221(6):734–741, discussion 731–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Panjala C, Nguyen JH, Al-Hajjaj AN, Rosser BA, Nakhleh RE, Bridges MD, Ko SJ, Buskirk SJ, Kim GP, Harnois DM (2012) Impact of neoadjuvant chemoradiation on the tumor burden before liver transplantation for unresectable cholangiocarcinoma. Liver Transpl 18(5):594–601

    Article  PubMed  Google Scholar 

  • Patkowski W, Stankiewicz R, Grat M, Krasnodebski M, Kornasiewicz O, Krawczyk M (2014) Poor outcomes after liver transplantation in patients with incidental cholangiocarcinoma irrespective of tumor localization. Transplant Proc 46(8):2774–2776

    Article  CAS  PubMed  Google Scholar 

  • Patt YZ, Hassan MM, Lozano RD, Brown TD, Vauthey JN, Curley SA, Ellis LM (2003) Phase II trial of systemic continuous fluorouracil and subcutaneous recombinant interferon Alfa-2b for treatment of hepatocellular carcinoma. J Clin Oncol 21(3):421–427

    Article  CAS  PubMed  Google Scholar 

  • Pavel M, Baudin E, Couvelard A, Krenning E, Oberg K, Steinmuller T, Anlauf M, Wiedenmann B, Salazar R, Barcelona Consensus Conference Participants (2012) ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 95(2):157–176

    Article  CAS  PubMed  Google Scholar 

  • Pfeiffenberger J, Koschny R, Hoffmann K, Mehrabi A, Schmitz A, Radeleff B, Stremmel W, Schemmer P, Ganten TM (2013) Sorafenib treatment is save and may affect survival of recurrent hepatocellular carcinoma after liver transplantation. Langenbecks Arch Surg 398(8):1123–1128

    Article  PubMed  Google Scholar 

  • Pokorny H, Gnant M, Rasoul-Rockenschaub S, Gollackner B, Steiner B, Steger G, Steininger R, Muhlbacher F (2005) Does additional doxorubicin chemotherapy improve outcome in patients with hepatocellular carcinoma treated by liver transplantation? Am J Transplant 5(4 Pt 1):788–794

    Article  CAS  PubMed  Google Scholar 

  • Rea DJ, Heimbach JK, Rosen CB, Haddock MG, Alberts SR, Kremers WK, Gores GJ, Nagorney DM (2005) Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg 242(3):451–458, discussion 458–461

    PubMed  PubMed Central  Google Scholar 

  • Roayaie S, Schwartz JD, Sung MW, Emre SH, Miller CM, Gondolesi GE, Krieger NR, Schwartz ME (2004) Recurrence of hepatocellular carcinoma after liver transplant: patterns and prognosis. Liver Transpl 10(4):534–540

    Article  PubMed  Google Scholar 

  • Rosen CB, Heimbach JK, Gores GJ (2008) Surgery for cholangiocarcinoma: the role of liver transplantation. HPB 10(3):186–189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saab S, Mctigue M, Finn RS, Busuttil RW (2010) Sorafenib as adjuvant therapy for high-risk hepatocellular carcinoma in liver transplant recipients: feasibility and efficacy. Exp Clin Transplant 8(4):307–313

    PubMed  Google Scholar 

  • Santoro A, Rimassa L, Borbath I, Daniele B, Salvagni S, Van Laethem JL, Van Vlierberghe H, Trojan J, Kolligs FT, Weiss A, Miles S, Gasbarrini A, Lencioni M, Cicalese L, Sherman M, Gridelli C, Buggisch P, Gerken G, Schmid RM, Boni C, Personeni N, Hassoun Z, Abbadessa G, Schwartz B, Von Roemeling R, Lamar ME, Chen Y, Porta C (2013) Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol 14(1):55–63

    Article  CAS  PubMed  Google Scholar 

  • Schwartz JD, Beutler AS (2004) Therapy for unresectable hepatocellular carcinoma: review of the randomized clinical trials-II: systemic and local non-embolization-based therapies in unresectable and advanced hepatocellular carcinoma. Anticancer Drugs 15(5):439–452

    Article  CAS  PubMed  Google Scholar 

  • Shetty K, Dash C, Laurin J (2014) Use of adjuvant sorafenib in liver transplant recipients with high-risk hepatocellular carcinoma. J Transplant 2014:913634

    Article  PubMed  PubMed Central  Google Scholar 

  • Soderdahl G, Backman L, Isoniemi H, Cahlin C, Hockerstedt K, Broome U, Makisalo H, Friman S, Ericzon BG (2006) A prospective, randomized, multi-centre trial of systemic adjuvant chemotherapy versus no additional treatment in liver transplantation for hepatocellular carcinoma. Transpl Int 19(4):288–294

    Article  PubMed  Google Scholar 

  • Sposito C, Mariani L, Germini A, Flores Reyes M, Bongini M, Grossi G, Bhoori S, Mazzaferro V (2013) Comparative efficacy of sorafenib versus best supportive care in recurrent hepatocellular carcinoma after liver transplantation: a case–control study. J Hepatol 59(1):59–66

    Article  CAS  PubMed  Google Scholar 

  • Staufer K, Fischer L, Seegers B, Vettorazzi E, Nashan B, Sterneck M (2012) High toxicity of sorafenib for recurrent hepatocellular carcinoma after liver transplantation. Transpl Int 25(11):1158–1164

    Article  CAS  PubMed  Google Scholar 

  • Stone MJ, Klintmalm GB, Polter D, Husberg BS, Mennel RG, Ramsay MA, Flemens ER, Goldstein RM (1993) Neoadjuvant chemotherapy and liver transplantation for hepatocellular carcinoma: a pilot study in 20 patients. Gastroenterology 104(1):196–202

    CAS  PubMed  Google Scholar 

  • Strosberg JR, Cheema A, Kvols LK (2011) A review of systemic and liver-directed therapies for metastatic neuroendocrine tumors of the gastroenteropancreatic tract. Cancer Control 18(2):127–137

    PubMed  Google Scholar 

  • Stuart K, Tessitore J, Huberman M (1996) 5-Fluorouracil and alpha-interferon in hepatocellular carcinoma. Am J Clin Oncol 19(2):136–139

    Article  CAS  PubMed  Google Scholar 

  • Sudan D, Deroover A, Chinnakotla S, Fox I, Shaw B Jr, Mccashland T, Sorrell M, Tempero M, Langnas A (2002) Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant 2(8):774–779

    Article  PubMed  Google Scholar 

  • Teng CL, Hwang WL, Chen YJ, Chang KH, Cheng SB (2012) Sorafenib for hepatocellular carcinoma patients beyond Milan criteria after orthotopic liver transplantation: a case control study. World J Surg Oncol 10:41

    Article  PubMed  PubMed Central  Google Scholar 

  • Truesdale AE, Caldwell SH, Shah NL, Argo CK, Al-Osaimi AM, Schmitt TM, Northup PG (2011) Sorafenib therapy for hepatocellular carcinoma prior to liver transplant is associated with increased complications after transplant. Transpl Int 24(10):991–998

    Article  CAS  PubMed  Google Scholar 

  • Vagefi PA, Hirose R (2010) Downstaging of hepatocellular carcinoma prior to liver transplant: is there a role for adjuvant sorafenib in locoregional therapy? J Gastrointest Cancer 41(4):217–220

    Article  PubMed  PubMed Central  Google Scholar 

  • Vitale A, Volk ML, Pastorelli D, Lonardi S, Farinati F, Burra P, Angeli P, Cillo U (2010) Use of sorafenib in patients with hepatocellular carcinoma before liver transplantation: a cost-benefit analysis while awaiting data on sorafenib safety. Hepatology 51(1):165–173

    Article  CAS  PubMed  Google Scholar 

  • Waghray A, Balci B, El-Gazzaz G, Kim R, Pelley R, Narayanan Menon KV, Estfan B, Romero-Marrero C, Aucejo F (2013) Safety and efficacy of sorafenib for the treatment of recurrent hepatocellular carcinoma after liver transplantation. Clin Transplant 27(4):555–561

    Article  CAS  PubMed  Google Scholar 

  • Welker MW, Bechstein WO, Zeuzem S, Trojan J (2013) Recurrent hepatocellular carcinoma after liver transplantation – an emerging clinical challenge. Transpl Int 26(2):109–118

    Article  PubMed  Google Scholar 

  • Xu J, Shen ZY, Chen XG, Zhang Q, Bian HJ, Zhu P, Xu HY, Song F, Yang XM, Mi L, Zhao QC, Tian R, Feng Q, Zhang SH, Li Y, Jiang JL, Li L, Yu XL, Zhang Z, Chen ZN (2007) A randomized controlled trial of Licartin for preventing hepatoma recurrence after liver transplantation. Hepatology 45(2):269–276

    Article  CAS  PubMed  Google Scholar 

  • Yeo W, Mok TS, Zee B, Leung TW, Lai PB, Lau WY, Koh J, Mo FK, Yu SC, Chan AT, Hui P, Ma B, Lam KC, Ho WM, Wong HT, Tang A, Johnson PJ (2005) A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst 97(20):1532–1538

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama I, Carr B, Saitsu H, Iwatsuki S, Starzl TE (1991) Accelerated growth rates of recurrent hepatocellular carcinoma after liver transplantation. Cancer 68(10):2095–2100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoon DH, Ryoo BY, Ryu MH, Lee SG, Hwang S, Suh DJ, Lee HC, Kim TW, Ahn CS, Kim KH, Moon DB, Kang YK (2010) Sorafenib for recurrent hepatocellular carcinoma after liver transplantation. Jpn J Clin Oncol 40(8):768–773

    Article  PubMed  Google Scholar 

  • Zavaglia C, Airoldi A, Mancuso A, Vangeli M, Vigano R, Cordone G, Gentiluomo M, Belli LS (2013) Adverse events affect sorafenib efficacy in patients with recurrent hepatocellular carcinoma after liver transplantation: experience at a single center and review of the literature. Eur J Gastroenterol Hepatol 25(2):180–186

    Article  CAS  PubMed  Google Scholar 

  • Zhu AX, Kudo M, Assenat E, Cattan S, Kang YK, Lim HY, Poon RT, Blanc JF, Vogel A, Chen CL, Dorval E, Peck-Radosavljevic M, Santoro A, Daniele B, Furuse J, Jappe A, Perraud K, Anak O, Sellami DB, Chen LT (2014a) Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA 312(1):57–67

    Article  PubMed  Google Scholar 

  • Zhu AX, Ryoo BY, Yen C, Kudo M (2014b) Ramucirumab as second-line treatment in patients withadvanced hepatocellular carcinoma following first-line therapywith sorafenib: results from the randomized phase III REACH study. In: ESMO congress, LBA16, Shanghai, China

    Google Scholar 

  • Zhu AX, Rosmorduc O, Evans TR, Ross PJ, Santoro A, Carrilho FJ, Bruix J, Qin S, Thuluvath PJ, Llovet JM, Leberre MA, Jensen M, Meinhardt G, Kang YK (2015) SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol 33(6):559–566

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Medical Oncology, Thomas Jefferson University Hospital, 1025 Walnut Street, 700 College, 19107, Philadelphia, PA, USA

    Jascha Rubin & Ashwin Sama

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  1. Jascha Rubin
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  2. Ashwin Sama
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Correspondence to Jascha Rubin .

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Editors and Affiliations

  1. Nicoletti Family Professor of Transplant Surgery, Director, Jefferson Transplant Institute, Director, Division of Transplantation, Surgical Director, Kimmel Cancer Center – Jefferson Liver Tumor Center, Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA

    Cataldo Doria

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© 2017 Springer International Publishing Switzerland

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Rubin, J., Sama, A. (2017). Systemic Chemotherapy in Orthotopic Liver Transplantation. In: Doria, C. (eds) Contemporary Liver Transplantation. Organ and Tissue Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-07209-8_14

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  • DOI: https://doi.org/10.1007/978-3-319-07209-8_14

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-07208-1

  • Online ISBN: 978-3-319-07209-8

  • eBook Packages: MedicineReference Module Medicine

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